Antimicrobial crosslinked polymers containing biomass derived materials

ABSTRACT

Novel, crosslinked polymers using biomass derived materials, such as aldaric acids and derivatives, are provided. The polymers can be used as hydrogels and in antimicrobial compositions.

This application is a Divisional of U.S. application Ser. No.11/064,191, now granted, filed on Feb. 23, 2005.

FIELD OF INVENTION

The invention is directed to the preparation of novel, crosslinkedpolymers using biomass derived materials, such as aldaric acids andderivatives. These polymers can be used as hydrogels.

BACKGROUND

The concept of using biomass-derived materials to produce other usefulproducts has been explored since man first used plant materials andanimal fur to make clothing and tools. Biomass derived materials havealso been used for centuries as adhesives, solvents, lighting materials,fuels, inks/paints/coatings, colorants, perfumes and medicines.Recently, people have begun to explore the possibility of using “refinedbiomass” as starting materials for chemical conversions leading to novelhigh value-in-use products. Over the past two decades, the cost ofrenewable biomass materials has decreased to a point where many arecompetitive with those derived from petroleum. In addition, manymaterials that cannot be produced simply from petroleum feedstocks arepotentially available from biomass or refined biomass. Many of theseunique, highly functionalized, molecules would be expected to yieldproducts unlike any produced by current chemical processes. “Refinedbiomass” is purified chemical compounds derived from the first or secondround of plant biomass processing. Examples of such materials includecellulose, sucrose, glucose, fructose, sorbitol, erythritol, and variousvegetable oils.

A particularly useful class of refined biomass is that of aldaric acids.Aldaric acids, also known as saccharic acids, are diacids derived fromnaturally occurring sugars. When aldoses are exposed to strong oxidizingagents, such as nitric acid, both the aldehydic carbon atom and thecarbon bearing the primary hydroxyl group are oxidized to carboxylgroups. An attractive feature of these aldaric acids includes the use ofvery inexpensive sugar based feedstocks, which provide low raw materialcosts and ultimately could provide low polymer costs if the properoxidation processes are found. Also, the high functional density ofthese aldaric acids provide unique, high value opportunities, which arecompletely unattainable at a reasonable cost from petroleum basedfeedstocks.

Hydrogels (hydrated gel) are polymers that contain water-swellable,three-dimensional networks of macromolecules held together by covalentor noncovalent (e.g., ionic or hydrogen bonded) crosslinks. Uponplacement in an aqueous environment, these networks swell to the extentallowed by the degree of crosslinking. They are used in many fields suchas medical applications, personal care formulations, coatings, andsurfactants.

U.S. Pat. No. 5,496,545 discloses crosslinked polyallylamine andpolyethyleneimine. The crosslinking agents disclosed includeepichlorohydrin, diepoxides, diisocyanates, α,ω-dihaloalkanes,diacrylates, bisacrylamides, succinyl chloride, and dimethyl succinate.The present invention provides new crosslinked polymers that canfunction as hydrogels. The polymers comprise crosslinking moieties thatcan be derived from biomass sources.

SUMMARY OF THE INVENTION

One aspect of the present invention is a crosslinked polymer comprising:

a linear, branched or cyclic polymeric backbone comprising repeat unitsthat comprise one or more of each of: hydrocarbylene groups,heteroatoms, and carbonyl carbon groups; wherein the hydrocarbylenegroups are aliphatic or aromatic, linear, branched, or cyclic, and caninclude combinations of aliphatic, aromatic, linear, branched and/orcyclic hydrocarbylene groups; and

one or more crosslinking units containing at least one aldaroylstructural unit of Formula I:

-   -   where n is 1-6.

The hydrocarbylene groups and heteroatoms of the repeat units areoptionally substituted with substituents that comprise one or more ofC₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonyl carbon groups,wherein the hydrocarbylene groups of the substituents are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof.

Preferably the crosslinking units are one or more of Formulae II, III,IV, and V:

wherein Q is —O— or —NH—, or salts thereof, and R₁, R₂, R₃ and R₄ arealiphatic or aromatic hydrocarbylene groups, linear, branched or cyclic,optionally substituted, and optionally containing —O—, —Si(ZZ′)O—,—(C═O)— or —NZ— linkages, where Z and Z′ are independently hydrogen,alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, orsubstituted aryl;

and wherein Formulae II, III, IV, and V are directly attached to thepolymer backbone.

Another aspect of the present invention is a crosslinked polymerprepared by a process comprising contacting a crosslinking agent with asubstrate polymer to form a crosslinked polymer, wherein thecrosslinking agent is one or more of Formulae VI, VII and VIII:

wherein L and L′ independently contain a suitable functional group, andn=1-6, m=0-4, and p=1-4;

and the substrate polymer comprises:

a linear, branched or cyclic polymeric backbone comprised of repeatunits that comprise one or more of hydrocarbylene groups, heteroatoms,and carbonyl carbon groups

-   -   wherein the hydrocarbylene groups are aliphatic or aromatic,        linear, branched, or cyclic, or combinations thereof; and

reactive pendant groups attached to the polymeric backbone, the pendantgroups being of the formula -G or —R-G.

-   -   wherein G is a nucleophile or electrophile;    -   wherein R is independently linear, cyclic, or branched        alkylene, arylene, or alkarylene groups of 1-22 carbon atoms,        optionally substituted with alkyl, aryl, hydroxy, amino,        carbonyl, ester, amide, alkoxy, nitrile or halogen, and        optionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ— linkages,        where Z and Z′ are independently hydrogen, alkyl, substituted        alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.        The hydrocarbylene groups and heteroatoms of the repeat units        are optionally substituted with substituents that comprise one        or more of C₁-C₃₀ hydrocarbylene groups, heteroatoms, and        carbonyl carbon groups. The hydrocarbylene groups of the        substituents can be aliphatic or aromatic, linear, branched, or        cyclic, or combinations thereof. Preferably, L and L′ are        derived from an amine, hydroxyl, carboxylic acid, ester,        urethane, urea, amide, or isocyanate; and G is an epoxide,        isocyanate, benzylic halide, amine, acid halide, ester, or        amide. Also preferably L and L′ are selected from optionally        substituted —NHR″, —OR″, and hydrocarbylene-C(═O)OR″ and G is        selected from —NH₂, —C(═O)Cl, —C(═O)OR″, or —C(═O)NH—R″—NH₂;        wherein R″ is independently an optionally substituted        hydrocarbyl or hydrocarbylene, and wherein n=2-4, m=0-1, and        p=2-3. The optional substituents on R″ can be any        heteroatom-containing group that does not participate directly        in reactions between the substrate polymer and the crosslinking        agent; i.e., the substituent is preferably not displaced during        such reaction and does not form a covalent bond with the        substrate polymer. Groups attached to the polymer by reaction        with G can contain aza (—NZ—) or ether (—O—) linkages (e.g., G        can be PEGylated). In one embodiment of the process, less than        100% of the reactive pendant groups are derivatized such that        the derivatized pendant groups are substantially unreactive to        the crosslinking agent. “Substantially unreactive”, as used        herein, means having a rate of reaction, e.g., with the        crosslinking agent, of about 20% or less of the rate of reaction        of an underivatized pendant group under the same conditions. The        derivatization can be performed before, during or after contact        of the crosslinking group with the polymer substrate.        Preferably, the reactive pendant groups are derivatized to        contain an optionally substituted aliphatic carbon chain with        optional —(NZ)—, and —O— linkages, where Z is hydrogen,        optionally substituted alkyl or optionally substituted aryl.

In another embodiment, the crosslinking agent is derived from an aldaricacid, aldarolactone, aldarodilactone, aldarolactone ester, aldaric acidmonoester, aldaric acid diester, or aldaramide, or salts thereof, andthe substrate polymer comprises polyallylamine, polyallylaminehydrochloride, branched polyethyleneimine, branched polyethyleneiminehydrochloride, poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(ω-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or derivativesor salts thereof. By “derived from” is meant that the crosslinking agentcan be produced from a starting compound in about six or fewer chemicalreaction steps, and retains an aldaric structure —C(═OXCHOR)_(n)C(═O)—wherein R is H or a carbon-containing group such as alkyl.

Preferably the crosslinking agent is one or more of the Formulae IX, X,XI, and XII:

wherein A1 is selected from:

and salts thereof;

and A2 is selected from

—NH—R₅—NH—

—NH—R—O—

and

—O—R—O—

and salts thereof;

wherein R₅ and R₇ are independently aliphatic or aromatic hydrocarbylenegroups, linear, branched or cyclic, optionally substituted, andoptionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ— linkages, where Zand Z′ are independently hydrogen, alkyl, substituted alkyl, alkaryl,substituted alkaryl, aryl, or substituted aryl; and R₆ is hydrogen or a1-22 carbon alkyl group.

The polymers and processes can be used to form compositions,emulsifiers, thickeners, and personal care products comprising thepolymers. Examples of personal care products that can be made from thepolymers include skin and hair conditioners. In some embodiments, thepolymers or products made therefrom are antimicrobial.

Other aspects of the invention include a method of cleaning andsmoothing human skin and a method of conditioning hair comprising theapplication of an effective amount of the polymers of the invention.Also included are methods for killing, inhibiting, or preventing thegrowth of at least one microbe, the method comprising contacting themicrobe with an effective amount of a crosslinked polymer according tothe invention, a method of reducing microbial population on a surfacecomprising contacting a surface with an effective amount of thecrosslinked polymer for a time sufficient to reduce the microbialpopulation on the surface, an antimicrobial substrate comprising acrosslinked polymer according to the invention that is bound to orincorporated into the substrate, and articles comprising suchantimicrobial substrates.

These and other aspects of the present invention will be apparent to oneskilled in the art, in view of the following description and theappended claims.

DETAILED DESCRIPTION

The following definitions may be used for the interpretation of thepresent specification and the claims:

By hydrocarbyl is meant a straight chain, branched or cyclic arrangementof carbon atoms connected by single, double, or triple carbon-to-carbonbonds, and substituted accordingly with hydrogen atoms. Hydrocarbylgroups can be aliphatic and/or aromatic. Examples of hydrocarbyl groupsinclude methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl,methylcyclohexyl, benzyl, phenyl, o-toluyl, m-toluyl, p-toluyl, xylyl,vinyl, allyl, butenyl, cyclohexenyl, cyclooctenyl, cyclooctadienyl, andbutynyl. Examples of substituted hydrocarbyl groups include toluyl,chlorobenzyl. —(CH₂)—O—(CH₂)—, fluoroethyl, p-(CH₃S)C₆H₅,2-methoxypropyl, and (CH₃)₃SiCH₂.

“Alkyl” means a saturated hydrocarbyl group. Examples of alkyl groupsinclude methyl, ethyl, propyl, isopropyl, butyl, s-butyl, isobutyl,pentyl, neopentyl, hexyl, heptyl, isoheptyl, 2-ethyihexyl, cyclohexyland octyl.

“Aryl” means a group defined as a monovalent radical formed conceptuallyby removal of a hydrogen atom from a hydrocarbon that is structurallycomposed entirely of one or more benzene rings. Examples of aryl groupsinclude benzene, biphenyl, terphenyl, naphthalene, phenyl naphthalene,and naphthylbenzene.

“Alkaryl” means an alkylated aryl group; that is, an aryl group asdefined above that is substituted with an alkyl group.

By “hydrocarbylene,” “alkylene,” “arylene,” or “alkarylene” is meant thedivalent form of the corresponding group.

“Substituted” means that a group contains one or more substituentgroups, or “substituents,” that do not cause the compound to be unstableor unsuitable for the use or reaction intended. Unless otherwisespecified herein, when a group is stated to be “substituted” or“optionally substituted,” substituent groups that can be present includecarboxyl, carboxamido (including primary, secondary or tertiarycarboxamido), acylamino, alkoxycarbonylamino, sulfonylamino, cyano,alkoxy, alkoxycarbonyl, acyloxy, fluoro, chloro, bromo, iodo, amino(including primary, secondary and tertiary amino), hydroxy, alkenyl,oxo, imino, hydroxyimino, hydrocarbyloxyimino, wherein the hydrocarbylgroup can be aliphatic, aryl or a combination of the two,trihydrocarbylsilyl, wherein each hydrocarbyl group can be independentlyalkyl or aryl, trihydrocarbylsiloxy, wherein each hydrocarbyl group canbe independently alkyl or aryl, nitro, nitroso, hydrocarbylthio, whereinthe hydrocarbyl group can be aliphatic, aryl or a combination of thetwo, hydrocarbylsulfonyl, wherein the hydrocarbyl group can bealiphatic, aryl or a combination of the two, hydrocarbylsulfinyl,wherein the hydrocarbyl group can be aliphatic, aryl or a combination ofthe two, hydrocarbyloxysulfonyl, wherein the hydrocarbyl group can bealiphatic, aryl or a combination of the two, sulfonamido (includingprimary, secondary and tertiary sulfonamido), sulfonyl,dihydrocarbylphosphino, wherein each hydrocarbyl group can beindependently alkyl or aryl, dihydrocarbyloxyphosphino, wherein eachhydrocarbyl group can be independently alkyl or aryl,hydrocarbylphosphonyl, wherein the hydrocarbyl group can be aliphatic,aryl or a combination of the two, hydrocarbyloxyphosphonyl, wherein thehydrocarbyl group can be aliphatic, aryl or a combination of the two,phosphonamido (including primary, secondary and tertiary phosphonamido),and salts of the aforementioned.

The present invention is directed to a crosslinked polymer comprising apolymeric backbone and one or more crosslinking units containing atleast one aldaroyl unit.

The polymer comprises:

A) a linear, branched or cyclic polymeric backbone comprising repeatunits that comprise one or more groups selected from hydrocarbylenegroups, heteroatoms, and carbonyl carbon groups, wherein thehydrocarbylene groups are aliphatic or aromatic, linear, branched, orcyclic, or combinations thereof; and

B) one or more crosslinking units containing at least one aldaroylstructural unit of Formula I:

-   -   where n is 1-6.

The hydrocarbylene groups and heteroatoms of the repeat units areoptionally substituted with substituents that comprise one or more ofC₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonyl carbon groups,wherein the hydrocarbylene groups of the substituents are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof.

The crosslinker shown in Formula I is attached to the polymer backbonevia the available valences at either end of the structural unit. Theyare attached either directly with no other atoms between the structureof Formula I and the backbone of the polymer, or indirectly with otheratoms or structural groups between Formula I and the polymer backbone.For example, in one embodiment shown below, the crosslinking unit (inwhich n=4) is indirectly attached to the polyethylene backbone via the—NH—CH₂—C(═O)—NH—CH₂— structural unit:

Aldaric acids are diacids derived from naturally occurring sugars. Whenaldoses are exposed to strong oxidizing agents, such as nitric acid,both the aldehydic carbon atom and the carbon bearing the primaryhydroxyl group are oxidized to carboxyl groups. This family of diacidsis known as aldaric acids (or saccharic acids). An aldarolactone has onecarboxylic acid lactonized; the aldarodilactone has both lactonized. Asillustration, the aldaric acid derivatives starting from D-glucose areshown below.

Any stereoisomer or mixture of stereoisomers can be used in thecompositions and processes disclosed herein. The aldaric acid derivativecan be glucaric acid or galactaric acid, or their derivatives such as,for example, glucarolactone, glucarodilactone, galactarolactone, anddimethyl galactarate.

The polymeric backbone can contain —NZ—, —N⁺ZZ′—, —O—, —C(═O)NZ—,—C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)NZ—, —NZC(═O)NZ′—, or—SiZZ′O—linkages, where Z and Z′ are independently hydrogen, alkyl,substituted alkyl, aryl, or substituted aryl. Substituents on the repeatunits contain one or more of —X, —O(Z), —N(ZZ′), —N⁺(ZZ′Z″), —C(═O)OZ,—C(═O)X, —C(═O)NZZ′, —C═N═O, —O—, —N(Z)—, —N⁺(ZZ′)—, —C(═O)N(Z)—,—C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)N(Z)—, —N(Z)C(═O)N(Z′)—,—C(═O)NH(CH₂)_(p)NH₂, —Si(ZZ′)O—, —(OCH₂CH₂)_(m)OH, or—(OSi(ZZ′))_(n)OH, or salts thereof, wherein X is a halogen, Z, Z′, andZ″ are independently hydrogen or C₁-C₂₂ optionally substituted alkyl oraryl, and wherein m is 1 to 50, n is 1 to 100, and p is 1 to 12.

The repeat units of the crosslinked polymer preferably comprisealiphatic hydrocarbylene groups with substituents comprising one or moreof aminoalkyl groups, —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, or—C(═O)NH(CH₂)_(p)NH₂, or salts thereof. The repeat units are alsopreferably azahydrocarbylenes or salts thereof, with one or moreterminal aminoalkyl groups or salts thereof as substituents on thenitrogen of the azahydrocarbylene repeat unit. Also preferably therepeat units contain substituents comprising one or more of C₁-C₂₂aminoalkyl groups, optionally substituted with alkyl or aldaroyl groupsor salts thereof. The aldaroyl moiety in the crosslinking unit ispreferably glucaroyl, galactaroyl, mannaroyl, xylaroyl, or tartaroyl.

In one embodiment, the crosslinked polymer is a derivative ofpolyallylamine, polyallylamine hydrochloride, branchedpolyethyleneimine, branched polyethyleneimine hydrochloride,poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(ω-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or a derivativeor salt thereof. For example, polymers having amine groups can have someof the amine groups alkylated, acylated, sulfonated, or reacted to formimines or aminals. Also, they can be in one or more salt forms orpartial salt forms, e.g., polyallyamine hydrochloride can be convertedto its p-toluenesulfonic acid or acetic acid salt. Polymers with acylchloride groups can be partially reacted with a monofunctional alcoholor amine to form ester or amide side chains. Such derivatives retain thebackbone structure and preferably some of the reactive side chainstructure as the original polymer from which the derivative is derived.The crosslinked polymer can additionally comprise one or more of thecrosslinking units of Formulae II, III, IV, or V:

wherein Q is —O— or —NH—, or a salt thereof, and R₁, R₂, R₃ and R₄ arealiphatic or aromatic hydrocarbylene groups, linear, branched or cyclic,optionally substituted, and optionally containing —O—, —Si(ZZ′)O—,—(C═O)— or —NZ— linkages, where Z and Z′ are independently hydrogen,alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, orsubstituted aryl.

The crosslinking units shown by Formulae II, III, IV, and V are directlyattached to the polymer backbone via the available valences at eitherend of the structural units.

Preferably, R₁ is —[(CH₂)₀₋₂₂]—, —(CH₂)_(a)C₆H₁₀(CH₂)_(b)—,—(CH₂CH₂NH)₁₋₂₂CH₂CH₂—, —[(CH₂CH(Z′)O)₁₋₂₂(CH₂)₂₋₃]— wherein Z′ is H orCH₃, —C(O)NH(CH₂)₂₋₂₂—, or —(CH₂)_(a)(C₆H₄)(CH₂)_(b)—, wherein a=0-6 andb=0-6;

R₂ is —[(CH₂)₁₋₂₁]—, —CH(CH₃)—, —CH(isopropyl)-, —CH(isobutyl)-,—CH(CH(CH₃)CH₂CH₃)—, —CH(CH₂OH)—, —CH(CH₂CH₂SCH₃)—, —CH(CH(OH)CH₃)—,—CH(CH₂C₆H₅)—, —CH(CH₂C₆H₄OH)—, —CH(CH₂CONH₂)—, or —CH(CH₂CH₂CONH₂)—;

R₃ is —[(CH₂)₂₋₂₂]—, —[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—,—[(CH₂)₀₋₆C₆H₄(CH₂)₀₋₆]—, —[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—,—[CH₂CH(CH₃)[OCH₂CH(CH₃)]₁₋₂₁]—, —(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,—[CH₂CH(CH₃)[CH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z)]— whereinx+y+z=2-50, —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)]— whereinx+y+z=2-50,—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y))CH₂[OCH₂CH(CH₃)]_(z)—wherein x+y+z=2-10 and Z′ is H, methyl or ethyl,—[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)— whereinx+y+z=3-100, or —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)— orsalts thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionallysubstituted alkyl, aryl, or alkaryl; and

R₄ is —C(═O)—, —C₆H₄CH₂—, —(CH₂)₁₋₂₂Y′CH₂CH(OH)CH₂—, or—(CH₂)₁₋₂₂Y′C(O)CH(OH)CH₂—, wherein Y′ is O or NH.

The R₃ moieties,—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH)]_(z)—and —[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y))CH₂[OCH₂CH(CH₃)]_(z)—, aretrivalent and therefore can react to form crosslinked structures. Otherpolyalkylene, polyalkyleneoxide, and polyalkylenearyl structures can betrivalent, tetravalent, or higher multivalent. Therefore, when R₃ ismultivalent, the polymer of the instant invention can exist in amultivalent crosslinked structure with the empty valences on thepolyalkyleneoxide being endcapped by available functionalities such asamines.

Preferably about 0.1% to about 100% of the polymer backbone repeat unitsare connected to a crosslinking unit. More preferably about 1% to about30% of the polymer backbone repeat units are connected to a crosslinkingunit.

Also provided according to the invention are crosslinked polymersprepared by a process comprising contacting a crosslinking agent with asubstrate polymer to form a crosslinked polymer, wherein thecrosslinking agent is one or more of Formulae VI, VII and VIII:

and n=1-6, m=0-4, and p=1-4. Preferably n=2-4, m=0-1, and p=2-3.

The substrate polymer used in the instant process comprises a linear,branched or cyclic polymeric backbone. The backbone contains repeatunits that comprise one or more of hydrocarbylene groups, heteroatoms,and carbonyl carbon groups. The hydrocarbylene groups are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof. Thehydrocarbylene groups and heteroatoms of the repeat units are optionallysubstituted with substituents that comprise one or more of C₁-C₃₀hydrocarbylene groups, heteroatoms, and carbonyl carbon groups, whereinthe hydrocarbylene groups of the substituents are aliphatic or aromatic,linear, branched, or cyclic, or combinations thereof.

The polymeric backbone used in the process can contain —NZ—, —N⁺ZZ′—,—O—, —C(═O)NZ—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)NZ—, —NZC(═O)NZ′—,or —SiZZ′O— linkages, where Z and Z′ are independently hydrogen, alkyl,substituted alkyl, aryl, or substituted aryl.

The substituents on the repeat units are preferably one or more of —X,—O(Z), —N(ZZ′), —N⁺(ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O, —O—,—N(Z)—, —N⁺(ZZ′)—, —C(═O)N(Z)—, —C(═O)O—, —C(═O)—, —OC(═O)O—,—(OCH₂CH₂)_(m)OH, or —(OSi(ZZ′))_(n)OH, or salts thereof, where X is ahalogen, Z, Z′, and Z″ are independently hydrogen, C₁-C₂₂ optionallysubstituted alkyl, or C₁-C₂₂ optionally substituted aryl, and where m is1 to 50, n is 1 to 100, and p is 1 to 12. More preferably, thesubstituents comprise one or more of C₁-C₂₂ aminoalkyl groups,optionally substituted with alkyl or aldaroyl, or a salt thereof. Therepeat units preferably comprise aliphatic hydrocarbylene groups withsubstituents comprising one or more of aminoalkyl groups, —C(═O)OZ,—C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH₂)_(n)NH₂, or salts thereof, where Xis halogen, Z and Z′ are independently hydrogen, C₁-C₂₂ alkyl,substituted alkyl, aryl, or substituted aryl, and n=1-12.

The repeat unit can be an azahydrocarbylene or salt thereof with one ormore terminal amino groups or salts thereof as substituents on the N ofthe azahydrocarbylene repeat unit.

The substrate polymer can also comprise polyallylamine, polyallylaminehydrochloride, branched polyethyleneimine, branched polyethyleneiminehydrochloride, poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(ω-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or derivativesor salts thereof.

Attached to the polymeric backbone are reactive pendant groups of theformula -G or —R-G; where G is a nucleophile or electrophile; and whereR is independently linear, cyclic, or branched alkylene, arylene, oralkarylene groups of 1-22 carbon atoms, optionally substituted withalkyl, aryl, hydroxy, amino, carbonyl, ester, amide, alkoxy, nitrile orhalogen, and optionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ—linkages, where Z and Z′ are independently hydrogen, alkyl, substitutedalkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.

The terms, “electrophile” and “nucleophile,” are well known to thoseskilled in the art, and can be broadly defined as reactive chemicalmoieties that act as electron acceptors or electron donors respectively.Preferably, G is an epoxide, isocyanate, benzylic halide, amine, acidhalide, ester, or amide; more preferably G is —NH₂, —C(═O)Cl, —C(═O)OR″or —C(═O)NH—R″—NH₂ wherein R″ is independently hydrogen or an optionallysubstituted hydrocarbyl or hydrocarbylene. Most preferably G is —NH₂.

L and L′ are defined as containing a suitable functional group. Asuitable functional group is herein defined as a functional group thatreadily forms a covalent bond with the reactive pendant group. Thefunctional group employed depends upon the synthetic method used to makethe crosslinked polymer. The functional group can contain heteroatomssuch as O, N, S, and/or can be derived from a functional group such asan amine, hydroxyl, carboxylic acid, ester, urethane, urea, amide, orisocyanate. Particularly useful functional groups are those that containa —NH— group, a —C(═O)O— group, a —O— group, or salts thereof.Preferably, the suitable functional group is derived from an amine,hydroxyl, carboxylic acid, ester, urethane, urea, amide, or isocyanate.More preferably L and L′ are independently selected from —Y—R, wherein Yis O, NH, or S and R is alkyl, substituted alkyl, alkaryl, substitutedalkaryl, aryl, or substituted aryl. Also more preferably L and L′ areindependently selected from optionally substituted —NHR″, —OR″, andhydrocarbylene-C(═O)OR″; wherein R″ is an optionally substitutedhydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3.

As illustration, a crosslinker that is capped with a carboxylic acid asthe suitable functional group would be expected to react readily withavailable amine pendant groups on the polymeric backbone. A crosslinkerend-capped with a hydroxyl group or an amine as a functional group wouldnot be expected to react with the pendant amine functionality of thepolymeric backbone. However, if the subject polymer backbone had acarboxylic acid or an isocyanate as pendant functionality, then acrosslinker capped with an amine or a hydroxyl functional group couldreact with the pendant group of the polymeric backbone.

In another embodiment, less than 100%, preferably up to about 50%, andmore preferably up to about 20% of the reactive pendant groups arederivatized so that they are unreactive to the crosslinking agent. Thederivatization can be performed by contacting the reactive pendantgroups with a derivatizing reagent before, during or after contact ofthe crosslinker with the substrate polymer. Preferably, the reactivependant groups are derivatized before the contact of the crosslinkerwith the polymer substrate. The reactive pendant groups can bederivatized to contain an optionally substituted aliphatic carbon chainwith optional —(NZ)—, and —O— linkages, where Z is hydrogen, optionallysubstituted alkyl or optionally substituted aryl. Preferably, thereactive pendant groups are derivatized to contain a linear or branchedalkyl group of 1-22 carbon atoms, optionally substituted with —O—linkages, and optionally substituted with —NH₂, halogen, hydroxyl, orcarbonyl groups, or salts thereof, more preferably a C₁-C₂₂ alkyl group,most preferably a C₂-C₁₈ unsubstituted alkyl group.

The crosslinking agent can be derived from an aldaric acid,aldarolactone, aldarodilactone, aldarolactone ester, aldaric acidmonoester, aldaric acid diester, or aldaramides, or salts thereof.Preferably the crosslinking agent is derived from glucaric acid,galactaric acid, mannaric acid, xylaric acid or tartaric acid.

In another embodiment, the crosslinking agent is of the Formulae IX, X,XI, XII:

wherein A1 is selected from:

and salts thereof; and A2 is selected from

—NH—R₅—NH—

—NH—R₅—O—

and

—O—R₅—O—

and salts thereof. R₅ and R₇ are independently aliphatic or aromatichydrocarbylene groups, linear, branched or cyclic, optionallysubstituted with alkyl, aryl, hydroxy, amino, carbonyl, carboxyl, ester,amide, alkoxy, nitrile or halogen, or slats thereof, and optionallycontaining —O—, —Si(ZZ′)O—, —(C═O)— or —NZ— linkages, where Z and Z′ areindependently hydrogen, alkyl, substituted alkyl, alkaryl, substitutedalkaryl, aryl, or substituted aryl; and R₆ is hydrogen or a 1-22 carbonalkyl group.

Preferably, R₅ and R₇ are independently optionally substituted aliphaticcarbon chains with optional —(NZ)— or —O— linkages, wherein Z ishydrogen, optionally substituted alkyl or optionally substituted aryl.More preferably, R₅ and R₇ are independently linear, cyclic, or branchedalkylene groups of 1-10 carbon atoms, optionally substituted with—O-linkages, and optionally substituted with —NH₂ groups, or saltsthereof.

Also preferably, R₇ is —[(CH₂)₁₋₂₁]—, —CH(CH₃)—, —CH(isopropyl)-,—CH(isobutyl)-, —CH(CH(CH₃)CH₂CH₃)—, —CH(CH₂OH)—, —CH(CH₂CH₂SCH₃)—,—CH(CH(OH)CH₃)—, —CH(CH₂C₆H₅)—, —CH(CH₂C₆H₄OH)—, —CH(CH₂CONH₂)—, or—CH(CH₂CH₂CONH₂)—;

and

R₅ is —[(CH₂)₂₋₂₂]—, —[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—,—[(CH₂)₀₋₆C₆H₄(CH₂)₀₋₆]—, —[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—,—[CH₂CH(CH₃)[OCH₂CH(CH₃)]₁₋₂₁]—, —(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,—[CH₂CH(CH₃)[OCH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z)]— whereinx+y+z=2-50, —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)_(z)]—wherein x+y+z=2-50,—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—wherein x+y+z=2-10 and Z′ is H, methyl or ethyl,—[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)— whereinx+y+z=3-100, or —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)— orsalts thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionallysubstituted alkyl, aryl, or alkaryl.

Examples of polyoxaalkyleneamines that can be used include to thosebased on Jeffamine® polyether amines (Huntsman LLC, Salt Lake City,Utah). Examples of polytetramethylene glycols that can be used includethose based on Terethane® polytetramethyleneetherglycol (E. I. DuPont deNemours, Wilmington, Del.).

In some embodiments, about 0.0005 to about 0.5 molar equivalents ofcrosslinking agent per reactive pendant group can be used in theprocess. Preferably, from about 0.005 to about 0.5 molar equivalents ofcrosslinking agent are used per reactive pendant group, and morepreferably about 0.01 to 0.25 molar equivalents per reactive pendantgroup.

The processes can be run at any suitable temperature but preferably atabout 20° C. to about 100° C. The processes can be carried out in apolymer melt, but are preferably carried out in the presence of asolvent. The choice of solvent is not critical provided the solvent isnot detrimental to reactant or product. Preferred solvents includewater, dimethylformamide, dimethylformamide LiCl, dimethylacetamide,dimethylacetamide LiCl, ethanol, and methanol.

The polymers disclosed herein are suitable for use as hydrogels.Hydrogels (hydrated gels) are herein defined as materials that absorblarge quantities of liquid, i.e., greater than 2 mass equivalents ofliquid. They are usually water-swellable, three-dimensional networks ofmacromolecules held together by covalent or noncovalent crosslinks. Whenplaced in aqueous solution, the networks swell to the extent allowed bythe degree of crosslinking.

Hydrogels are useful in many applications, such as medical products,personal care formulations, exfoliants, humectants, surfactants,thickeners, anti-irritants, antimicrobials, lubricants, emulsifiers,delivery agents, coatings, and surfactants. In some embodiments thehydrogels are conducting. The polymers can be modified to introduce awide range of properties to make them more suitable in suchapplications. Additionally, divalent crosslinking agents as disclosedherein can be used as water-soluble chain extenders for polyurethanes,and hydroxylated block or comb copolymers made with the processesdescribed herein can be used as pigment dispersants. When used asco-polymers or modifiers to other polymeric materials, the polymers canimpart moisture wicking improvements, dyeability, and/or flameresistance to the other materials.

As used herein, the term “antimicrobial” means killing, or preventing orinhibiting the growth of, microorganisms, including bacteria and fungi.“Growth inhibition” means reduced rate of growth of a population ofmicroorganisms. “Growth prevention” means that growth is stopped.

Polymers described herein are also suitable for use in cosmeticproducts.

Also provided are methods for cleaning and/or smoothing human skincomprising the application of an effective amount of the polymersdescribed herein, and methods of conditioning hair comprising theapplication of an effective amount of the polymers described herein.

As used herein, “cosmetic products” are products intended for increasingthe appeal, visually and/or olfactorily, of the human body. Likewise,“personal care products” are products intended for cleaning, smoothingor otherwise improving the health, feel, or well-being of the outside ofthe human body. These definitions of cosmetic and personal care productsat least partially overlap since many products provide functions in bothcategories. Examples of cosmetic products are: perfumes and likeproducts known as “eau de toilette” and “eau de parfum,” hand and bodylotions, skin tonics, shaving products, bath and shower products,deodorant and antiperspirant products, hair care products such asshampoos and hair conditioners, and mouth and dental care products. Suchproducts are well known in the art. Thus, examples of skin care productsare described in “Harry's Cosmeticology,” R. G. Harry, 6^(th) edition,Leonard Hill Books (1973), Chapters 5-13, 18 and 35; examples ofdeodorants and antiperspirants are described in C. Fox, cosmetics andToiletries 100 (December 1985), pp 27-41; examples of hair care productsare described “Harry's Cosmeticololgy,” vide supra, chapters 25-27;examples of dental care products are described in M. Pader, OralHygiene: Products and Practice, Marcel Dekker, New York (1988).

For use in the personal care field, the polymers can be modified toenhance moisture retention, lubricity, static control, curl retention,sheen, and/or “body” in hair-care related products. For skin careproducts could the polymers can be used to make exfoliants (for example,as α-hydroxy acid replacements), humectants, surfactants, thickeners,anti-irritants, antimicrobials, lubricants, emulsifiers, and deliveryagents. The polymers can be used to make topical antimicrobialsubstances or barriers, or as additives to inhibit microbial growth in aseparate formulation, or may impart residual antimicrobial activity.Such residual antimicrobial activity can be imparted to a surface, forexample, by depositing the polymer onto the surface or by covalently orotherwise attaching the polymer to the surface. Examples of surfaces towhich the polymers can be applied include steel, and plastic, althoughsubstantially any surface can be treated by application of the polymers.Antimicrobial products containing the polymers can be applied to animalskin, including human skin.

Skin conditioning agents as herein defined include astringents, whichtighten skin; exfoliants, which remove exterior skin cells: emollients,which help maintain a smooth, soft, pliable feel and appearance;humectants, which increase the water content of the top layer of skin;occlusives, which retard evaporation of water from the skin's surface;and miscellaneous compounds that enhance the feel and/or appearance ofdry or damaged skin or reduce flaking and restore suppleness. Skinconditioning agents are well known in the art, and are disclosed, forexample, in Green et al. WO 0107009, and are available commercially fromvarious sources. Examples of skin conditioning agents includealpha-hydroxy acids, beta-hydroxy acids, polyols, hyaluronic acid,D,L-panthenol, polysalicylates, vitamin A palmitate, vitamin E acetate,glycerin, sorbitol, silicones, silicone derivatives, lanolin, naturaloils, and triglyceride esters.

The skin care, hair care, and hair coloring compositions made from thepolymers can also contain one or more conventional cosmetic ordermatological additives or adjuvants, such as, for example, fillers,surfactants, thixotropic agents, antioxidants, preserving agents, dyes,pigments, fragrances, thickeners, vitamins, hormones, moisturizers, UVabsorbing sunscreens, wetting agents, cationic, anionic, nonionic oramphoteric polymers, and hair coloring active substances. Such adjuvantsare well known in the field of cosmetics and are disclosed, for example,in “Harry's Cosmeticology.” 8^(th) edition, Martin Rieger, ed., ChemicalPublishing, New York (2000).

The polymers can also function as surface disinfectants, or asingredients in a formulation designed to function as a surfacedisinfectant.

For use in medical applications, the polymers can act as coatings thatretain moisture, lubricate, conduct electricity, facilitate sustainedrelease of therapeutic agents, absorb undesirable materials thataccumulate in the area of an implant, or act as local antimicrobialagents. The materials of the current invention can be used as componentsof polymeric medical adhesives (or anti-adhesives), as monomericcrosslinkers, and as components of adhesives that can be deactivated toprevent bandages from creating or enlarging sores on chronicallybandaged areas. In the area of medical devices, the polymers can be usedas biocompatible agents to attach antimicrobial, anti-inflammatory, oranti-proliferative agents to the surface of catheters, stents, or othermedical implants. Sustained release can be accomplished by slowdiffusion of at least one biologically active agent out of the polymerichydrogel matrix. Sustained release can further be facilitated by slowhydrolysis of the crosslink bonds.

In agriculture, uses for the polymers include use as seed coatings,microencapsulating agents (for lower toxicity, slow release, and/orchemical stability), surface tension modifying agents (to improvespreadability or wash-off resistance), or to improve water solubility ofnon-soluble active ingredients.

EXAMPLES

Unless otherwise stated, in the Examples, the abbreviations used havethe following meanings:

Abbreviation Ingredient Name 1BrC16 1-bromohexadecane 4,9-DODDA4,9-dioxa-1,12-dodecanediamine 9DA 1,9-diaminononane DMG dimethylgalactarate GA D-glucaric acid GDL D-glucaro-1,4:6,3-dilactone HMDA1,6-hexanediamine JEFF Jeffamine ® JEFF EDR-148 Jeffamine ®(H₂NCH₂CH₂OCH₂CH₂OCH₂CH₂NH₂) JEFF EDR-192 Jeffamine ®(H₂NCH₂CH₂(OCH₂CH₂)₃NH₂) JEFF T5000 Jeffamine ® polyethertriamine JEFFT403 Jeffamine ® polypropyleneoxytriamine PAlAmHCl polyallylamine HCl(obtained from Polysciences, Inc., Warrington, PA)

ANALYSES

Unless otherwise specified, the analyses were performed as follows.

Inherent Viscosity (η_(inh))

Inherent viscosities were generally run as 0.5% solutions in eitherhexafluoroisopropanol (HFIP) or m-cresol at 30° C.

Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis(TGA)

DSC and TGA studies of all polymers were conducted on 5-10 mg samplesrun at 10° C./min under nitrogen. Sample temperatures spanned rangesbeginning as low as −100° C. to as high as 300° C., depending on polymercharacter and stability. Samples were generally cooled after the firstheat cycle and a second heat cycle was then conducted. Generally,polymer DSC results reported are second heat results to eliminateartifacts of thermal history variations.

Swell Factor

Into a pre-dried, tared, 150 mL coarse fritted filter funnel was addedabout 1 g of polymer. The stem of the funnel was sealed with a rubberstopper. The funnel was placed on a filter flask and about 100 mL ofdistilled water at about 22° C. is added to the funnel. The contentswere stirred, if necessary, to fully disperse the water and polymer. Thecontents were then left undisturbed for 15 minutes. The rubber stopperwas then removed from the stem of the funnel, and suction was applied tothe funnel for 5 minutes. The stem and underside of the funnel were thenrinsed with ethanol to remove any remaining water droplets and suctionwas then continued for an additional 5 minutes. Any remaining waterdroplets were wiped off the funnel with a paper towel. The funnel andcontents were then weighed to determine the weight of water retained bythe polymer.

$\begin{matrix}{{{Swell}\mspace{14mu} {factor}} = \frac{\begin{matrix}{\left( {{{total}\mspace{14mu} {{wt}.\mspace{14mu} {of}}\mspace{14mu} {wet}\mspace{14mu} {polymer}} + {funnel}} \right) -} \\\left( {{{total}\mspace{14mu} {{wt}.\mspace{14mu} {of}}\mspace{14mu} {dry}\mspace{14mu} {polymer}} + {funnel}} \right)\end{matrix}}{{{wt}.\mspace{14mu} {of}}\mspace{14mu} {dry}\mspace{14mu} {polymer}}} \\{= \frac{\left( {{wet}\mspace{14mu} {{wt}.{- {dry}}}\mspace{14mu} {{wt}.}} \right)}{{dry}\mspace{14mu} {{wt}.}}} \\{= \frac{g\mspace{14mu} {water}\mspace{14mu} {retained}}{g\mspace{14mu} {polymer}}}\end{matrix}$

Solubility

Solubilities were generally determined using 0.01 g of test material in10 mL of test solvent. The vials containing the samples were constantlyagitated via a shaker tray at room temperature for anywhere between 24hours and 4 weeks. Solubility was determined by visual inspection todetermine sample homogeneity. Any variance in density gradient, orrefractive index was taken as indicating insolubility. Samples deemed tobe insoluble were shaken at room temperature for at least 1 week, and inmany cases were shaken for 2 weeks or more. A wide range of commonsolvent types was generally used to allow a broad range of polarity andsolvent parameters to come into play.

Film Properties

Film properties were determined on 0.25 inch×2 inch samples cut fromlarger films spread onto glass with a blade applicator. Generally, filmshad thicknesses of 5 mil or less. Film properties reported represent anaverage of at least five measurements for each sample.

The reactions depicted in the following Examples are meant to beillustrative only and not representative of exact structures.

Examples 1-28

Polymers were prepared by first dissolving polyallylamine hydrochlorideof ˜60,000 molecular weight in water. To that solution was added enoughsodium hydroxide to just neutralize the equivalent amount of ammoniumhydrochloride functions as would be used by the added GDL. To thepartially neutralized polyallylamine hydrochloride was added a watersolution of GDL at room temperature. The reaction was substantially overin a matter of minutes. A representative polymerization with GDL isshown below.

The crosslinking was performed using various compounds as describedbelow in a representative reaction with GDL. When another compound wasused in the in the crosslinking reaction along with the GDL, such as9DA, they were both added simultaneously. Into a 250-mL 3-necked roundbottom flask equipped with a heating mantle, reflux condenser, nitrogeninlet, and overhead stirrer was added 20 mL of water, 2.80 g (0.030equivalent, 60,000 MW) of polyallylamine HCl, and 0.26 g (0.0066 mol) ofsodium hydroxide. This mixture was stirred at room temperature until ahomogeneous solution was achieved (˜10 minutes). At this point, ahomogeneous solution prepared from 10 mL of water and 0.57 g (0.0033mol) of GDL was slowly poured at room temperature into the solutioncontaining the polyallylamine HCl. Within 1 to 2 minutes, gel hadformed. The gel was then allowed to stir for ˜2 hours at roomtemperature, after which time it was removed from the flask. The gel wasthen washed 3 times with 100 mL aliquots of methanol followed by THF.The gel was then dried in a vacuum oven at 80° C. to yield 2.79 g(89.1%) of a granular white hydrogel polymer. The results are shown inTable 1. The % crosslinking shown in Table 1 is a theoreticalcalculation of the % of total amine nitrogens (from the polyallylaminehydrochloride) tied up in the crosslinking process with the aldaricacid. The calculation was based on the total weight of polyallylaminehydrochloride used (molar equivalents of allylamine) and the total molarequivalents of the GDL added to the process. Total final crosslinkingwas not measured but is assumed since the polymer gelled and becameinsoluble, although NMR indicated that conversion was less than 100%.

When only 5-15% of the ammonium groups were allowed to react with GDL, avery viscous water solution resulted that could be cast into a film. Theresulting films were brittle, but less so than the startingpolyallylamine hydrochloride homopolymer. As more ammonium groupsreacted with GDL, gels eventually formed. Highly swellable hydrogels(with swell ratios as high as 90) were readily formed when ˜22% of theammonium hydrochloride equivalents were neutralized and GDL was added inan equivalent amount (˜11% since both ends of the molecule are assumedto react). The gels were optically clear and colorless. The data inTables 1 and 2 show some of the properties that can be obtained in thepolymers by varying the ingredients used in making them.

TABLE 1 Solvent/ % Ex. Composition Catalyst Media Color Yield Inh ViscInh Sol. Polym. Character Swell 1 PAlAmHCl/GDL (10:1) - 20%triethylamine Water white — insol HFIP Powder 4.72 crosslinking 2PAlAmHCl/GDL (8:1) - 25% triethylamine Water white — insol HFIP powder -very brittle 12.27 crosslinking film 3 PAlAmHCl/GDL (8.7:1) - 23%triethylamine Water white — insol HFIP powder - poor film 80.73crosslinking 4 PAlAmHCl/GDL (5:1) - 40% triethylamine Water off white90.1 insol HFIP Powder 48 crosslinking 5 PAlAmHCl/GDL (9.1:1) - 22%triethylamine Water white — insol HFIP powder - very brittle 28.1crosslinking film 6 PAlAmHCl/GDL (9.1:1) - 22% sodium Water white 89.1insol HFIP Powder 89.5 crosslinking hydroxide 7 PAlAmHCl/GDL (9.1:1) -22% calcium Water white 84.7 insol HFIP Powder 88.5 crosslinkinghydroxide 8 PAlAmHCl/GDL (9.1:1) - 22% calcium Water white — insol HFIPpowder - poor film, 6.36 crosslinking hydroxide very brittle 9PAlAmHCl/GDL (9.1:1) - 22% calcium Water white — insol HFIP powder -poor film, sol. in crosslinking hydroxide very brittle water 10PAlAmHCl/(GDL/JEFF EDR- sodium Water white 68.1 insol water powder -brittle, 71.3 148 (2:1)) - 20% crosslinking hydroxide clear film 11PAlAmHCl/(GDL/JEFF EDR- sodium Water white 92.9 insol water powder -brittle, 49 192 (2:1)) - 20% crosslinking hydroxide clear film 12PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 40 insol water Powder 40.1(3:1)) - 10% crosslinking hydroxide ethanol 13 PAlAmHCl/(GDL/JEFF T5000sodium water/ white 31.9 insol water Powder 8.04 (3:1)) - 20%crosslinking hydroxide ethanol 14 PAlAmHCl/(GDL/JEFF T5000 sodium water/white 28.4 insol water powder - poor film sol. in (3:1)) - 5%crosslinking hydroxide ethanol water 15 PAlAmHCl/(GDL/JEFF T5000 sodiumwater/ white — insol water powder - poor, sol. in (3:1)) - 1%crosslinking hydroxide ethanol clear, brittle film water 16PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 61.6 insol water powder -very poor 11 (3:1)) - 3% crosslinking hydroxide ethanol film 17PAlAmHCl/(GDL/JEFF T403 sodium Water white 69.4 insol water powder -poor, sol. in (3:1)) - 3% crosslinking hydroxide brittle film water 18PAlAmHCl/(GDL/JEFF T403 sodium Water white 74.2 insol water powder -poor, very sol. in (3:1)) - 5% crosslinking hydroxide brittle film water19 PAlAmHCl/(GDL/JEFF T403 sodium Water white 83.9 insol water powder -poor, 83.8 (3:1)) - 20% crosslinking hydroxide brittle film 20PAlAmHCl/(GDL/4,9-DODDA sodium Water white 77.4 insol water powder -clear film, 78.6 (2:1)) - 20% crosslinking hydroxide slightly flexible,fair 21 PAlAmHCl/(GDL/4,9-DODDA sodium Water light 77.2 insol waterpowder - very poor 26.7 (2:1)) - 25% crosslinking hydroxide yellow film22 PAlAmHCl/(GDL/(9DA/4,9- sodium water white 60 — — Powder 31.1 DODDA)(2:0.5:0.5)) - 20% hydroxide crosslinking 23 PAlAmHCl/(GDL/9DA (2:1)) -sodium Water white 63.6 — — Powder 23.7 20% crosslinking hydroxide 24PAlAmHCl/(GDL/9DA (2:1)) - sodium Water white — — — powder - fair film,75.2 15% crosslinking hydroxide slightly flexible 25 PAlAmHCl/(GDL/4,9-sodium Water tan — — — powder—poor, brittle 48.5 DODDA/9DA(2/0.5/0.5)) - hydroxide film 15% crosslinking 26PAlAmHCl/(GDL/4,9-DODDA sodium Water tan — — — powder - poor film 2(1.33:1)) hydroxide 27 PAlAmHCl/(GDL/9DA sodium Water off white — — —powder - poor film 1.29 (1.33:1)) hydroxide 28 PAlAmHCl/(GDL/9DA(2:1)) - sodium Water light 82.9 — — Powder 0.65 100% crosslinkinghydroxide yellow

TABLE 2 Ex. Composition Tg 1 (C.) Tg 2 (C.) Tg 3 (C.) Tm 1 (C.) ΔH (J/g)Tm 2 (C.) d H (J/g) Tm 3 (C.) d H (J/g) 1 PAlAmHCl/GDL (10:1) - — — —180.9 — — — — — 20% crosslinking 2 PAlAmHCl/GDL (8:1) - 25% — — — 190.97— — — — — crosslinking 3 PAlAmHCl/GDL (8.7:1) - — — — 191.23 7.544 — — —— 23% crosslinking 4 PAlAmHCl/GDL (5:1) - 40% — — — 192.38 17.99 — — — —crosslinking 5 PAlAmHCl/GDL (9.1:1) - — — — 196.63 5.076 — — — — 22%crosslinking 6 PAlAmHCl/GDL (9.1:1) - — — — 196.75 5.318 — — — — 22%crosslinking 7 PAlAmHCl/GDL (9.1:1) - — — — 251.32 15.99 — — — — 22%crosslinking 8 PAlAmHCl/GDL (9.1:1) - — — — 202.61 7.165 — — — — 22%crosslinking 9 PAlAmHCl/GDL (9.1:1) - — — — 165.56 1.245 — — — — 22%crosslinking 10 PAlAmHCl/(GDL/JEFF — — — 187 5.99 248.04 6.291 — —EDR-148 (2:1)) - 20% crosslinking 11 PAlAmHCl/(GDL/JEFF — — — — — — — —— EDR-192 (2:1)) - 20% crosslinking 12 PAlAmHCl/(GDL/JEFF — — — 188.451.008 251.86 4.542 — — T5000 (3:1)) - 10% crosslinking 13PAlAmHCl/(GDL/JEFF — — — 251.88 7.862 — — — — T5000 (3:1)) - 20%crosslinking 14 PAlAmHCl/(GDL/JEFF — — — 220.09 2.666 — — — — T5000(3:1)) - 5% crosslinking 15 PAlAmHCl/(GDL/JEFF 204.2 — — — — — — — —T5000 (3:1)) - 1% crosslinking 16 PAlAmHCl/(GDL/JEFF 102.6 215.5 — — — —— — — T5000 (3:1)) - 3% crosslinking 17 PAlAmHCl/(GDL/JEFF 224.4 — — — —— — — — T403 (3:1)) - 3% crosslinking 18 PAlAmHCl/(GDL/JEFF 170 232.3 —— — — — — — T403 (3:1)) - 5% crosslinking 19 PAlAmHCl/(GDL/JEFF 175.7227.5 — — — — — — — T403 (3:1)) - 20% crosslinking 20 PAlAmHCl/(GDL/4,9-168.8 234.4 204.7 1.281 — — — — DODDA (2:1)) - 20% crosslinking 21PAlAmHCl/(GDL/4,9- 171 209.5 247.6 — — — — — — DODDA (2:1)) - 25%crosslinking 22 PAlAmHCl/(GDL/(9DA/4,9- 174.4 — — — — — — — — DODDA)(2:0.5:0.5)) - 20% crosslinking 23 PAlAmHCl/(GDL/9DA 174.9 — — — — — — —— (2:1)) - 20% crosslinking 24 PAlAmHCl/(GDL/9DA 168.7 — — — — — — — —(2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- 142.5 174.2 — 224.280.261 — — — — DODDA/9DA (2/0.5/0.5)) - 15% crosslinking 26PAlAmHCl/(GDL/4,9- 45 216.6 — 103.33 177.97 23.69 188.41 16.3 DODDA(1.33:1)) 27 PAlAmHCl/(GDL/9DA 75.94 — — 152.48 12.17 165.25 31.69195.55 9.072 (1.33:1)) 28 PAlAmHCl/(GDL/9DA (2:1)) - — — — 167.03 4.206190.61 14.02 — — 100% crosslinking

TABLE 3 Tc 1 d H Tc 2 d H Tdec Sol. Sol. Sol. Sol. Sol. Sol. Sol. Ex.Composition (C.) (J/g) (C.) (J/g) (C.) H2O MeOH Toluene DMSO DMAC THFCH2CL2 1 PAlAmHCl/GDL (10:1) - — — — — 200 sol. insol. insol. insol.insol. insol. insol. 20% crosslinking 2 PAlAmHCl/GDL (8:1) - 25% — — — —200 insol. insol. insol. insol. insol. insol. insol. crosslinking 3PAlAmHCl/GDL (8.7:1) - — — — — 225 insol. insol. insol. insol. insol.insol. insol. 23% crosslinking 4 PAlAmHCl/GDL (5:1) - 40% — — — — 225insol. insol. insol. insol. insol. insol. insol. crosslinking 5PAlAmHCl/GDL (9.1:1) - — — — — 200 insol. insol. insol. insol. insol.insol. insol. 22% crosslinking 6 PAlAmHCl/GDL (9.1:1) - — — — — 225insol. insol. insol. insol. insol. insol. insol. 22% crosslinking 7PAlAmHCl/GDL (9.1:1) - — — — — 220 insol. insol. insol. insol. insol.insol. insol. 22% crosslinking 8 PAlAmHCl/GDL (9.1:1) - — — — — 210insol. insol. insol. insol. insol. insol. insol. 22% crosslinking 9PAlAmHCl/GDL (9.1:1) - — — — — 210 sol. insol. insol. insol. insol.insol. insol. 22% crosslinking 10 PAlAmHCl/(GDL/JEFF — — — — 210 — — — —— — — EDR-148 (2:1)) - 20% crosslinking 11 PAlAmHCl/(GDL/JEFF 223.419.953 — — 210 insol. insol. insol. insol. insol. insol. insol. EDR-192(2:1)) - 20% crosslinking 12 PAlAmHCl/(GDL/JEFF — — — — 200 insol.insol. insol. insol. insol. insol. insol. T5000 (3:1)) - 10%crosslinking 13 PAlAmHCl/(GDL/JEFF — — — — 210 insol. insol. insol.insol. insol. insol. insol. T5000 (3:1)) - 20% crosslinking 14PAlAmHCl/(GDL/JEFF — — — — 225 insol. insol. insol. insol. insol. insol.insol. T5000 (3:1)) - 5% crosslinking 15 PAlAmHCl/(GDL/JEFF — — — — 250sol. insol. insol. insol. insol. insol. insol. T5000 (3:1)) - 1%crosslinking 16 PAlAmHCl/(GDL/JEFF — — — — 235 insol. insol. insol.insol. insol. insol. insol. T5000 (3:1)) - 3% crosslinking 17PAlAmHCl/(GDL/JEFF — — — — 240 sol. insol. insol. insol. insol. insol.insol. T403 (3:1)) - 3% crosslinking 18 PAlAmHCl/(GDL/JEFF — — — — 240sol. insol. insol. insol. insol. insol. insol. T403 (3:1)) - 5%crosslinking 19 PAlAmHCl/(GDL/JEFF — — — — 225 insol. insol. insol.insol. insol. insol. insol. T403 (3:1)) - 20% crosslinking 20PAlAmHCl/(GDL/4,9- — — — — 200 insol. insol. insol. insol. insol. insol.insol. DODDA (2:1)) - 20% crosslinking 21 PAlAmHCl/(GDL/4,9- 284.771.116 — — 200 insol. insol. insol. insol. insol. insol. insol. DODDA(2:1)) - 25% crosslinking 22 PAlAmHCl/(GDL/(9DA/4,9- — — — — 225 insol.insol. insol. insol. insol. insol. insol. DODDA) (2:0.5:0.5)) - 20%crosslinking 23 PAlAmHCl/(GDL/9DA — — — — 225 insol. insol. insol.insol. insol. insol. insol. (2:1)) - 20% crosslinking 24PAlAmHCl/(GDL/9DA — — — — 225 insol. insol. insol. insol. insol. insol.insol. (2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- — — — — 175insol. insol. insol. insol. insol. insol. insol. DODDA/9DA(2/0.5/0.5)) - 15% crosslinking 26 PAlAmHCl/(GDL/4,9- — — — — 150 insol.insol. insol. insol. insol. insol. insol. DODDA (1.33:1)) 27PAlAmHCl/(GDL/9DA — — — — 150 insol. insol. insol. insol. insol. insol.insol. (1.33:1)) 28 PAlAmHCl/(GDL/9DA — — — — 150 — — — — — — — (2:1)) -100% crosslinking

Example 29 Synthesis of Modified Polyallylamine Crosslinked with GDL

Into a 2000-mL 3-necked flask equipped with a heating mantle, refluxcondenser, nitrogen inlet, and overhead stirrer was added 525 mL ofwater, 70 g of polyallylamine hydrochloride (0.749 mole equivalent ofamine), and 2.24 g (0.056 mol) of sodium hydroxide. After theseingredients dissolved. 17.08 g (0.056 mol) of 1-bromohexadecane wasadded. The reaction mixture was heated at reflux for 5 hours. Afterward,the reaction mixture was cooled to room temperature and stirredovernight. An additional 5.60 g (0.140 mol) of sodium hydroxide wasadded to the mixture. After the sodium hydroxide dissolved, 12.18 g(0.070 mol) of GDL dissolved in 175 mL of water was added to thereaction mixture. Almost immediately a gel formed. The gelled mixturewas then gently heated at 50° C. for about 7 hours. The gel wasfiltered, washed 3× with methanol, and then washed 3× with THF. It wasthen put into a vacuum oven set at 80° C. for at 24 hours to dry thepolymer. The pale yellow polymer (58.85 g, 60.5%) exhibited a swellratio of 7.9.

Example 30A Synthesis of Polyallylamine Crosslinked with DiethylTartrate

The preparation was conducted under nitrogen atmosphere with oven-driedglassware. Polyallylamine hydrochloride (MW ca. 60,000, 0.876 g, 9.36mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar, and water (2 mL) was added. Dropwise addition of anaqueous solution (1.0 mL) of sodium hydroxide (0.113 g, 2.83 mmol) tothe solution resulted in a viscous solution. A solution of diethylL-tartrate (0.240 mL, 1.40 mmol) in water (1.0 mL) was added and theresulting solution was stirred at ambient temperatures for 38 hours. Thegelled reaction mixture was washed with methanol (160 mL) to removesodium chloride. Vacuum-drying gave a white solid (0.86 g, 93% yield)that exhibited a swell ratio of 112.6 (determined after swollen gel wassubjected to 6 hours of dynamic suction followed by ˜28 hours of staticsuction).

Example 30B Synthesis of Polyallylamine Crosslinked with DiethylTartrate

Poly(allylamine hydrochloride), M_(w) 60,000 (42.04 g, 0.4493 mole ofamine groups) was dissolved overnight in 155 mL of water in a 3-neck500-mL round-bottom flask equipped with a magnetic stir bar. A solutionof 5.392 g (0.1348 mole) of sodium hydroxide in 25 mL of water was addeddropwise over a period of 10 minutes, using 2 mL of water to completethe transfer. To the resulting pale yellow syrup was added with stirringa solution of 13.897 g (67.40 mmoles) of diethyl L-tartrate in 10 mL ofwater, using 2 mL of water to complete the transfer. The reaction wasallowed to proceed for 4 days, during which the mixture gelled and themagnetic stir bar seized. The reaction mixture was combined with 250 mLof methanol to precipitate out the product. The resulting gummy solidwas separated from the liquid and triturated in a blender with 8successive 250-mL portions of methanol, decanting the methanol eachtime. The resulting solid was ground and dried under vacuum to give38.47 g (86% yield) of hydrogel that exhibited a swell factor of 224.

Example 31 Synthesis of Polyallylamine Crosslinked with GDL

The preparation was conducted in a drybox with oven-dried glassware.Polyallylamine hydrochloride (MW ca. 60,000, 6.88 g, 73.5 mmol) wasweighed into a 500-mL round-bottom flask equipped with a magneticstirbar. Methanol (285 mL) was added and the solution was treated withneat triethylamine (12.3 mL, 88.3 mmol) followed by dropwise addition ofa solution of GDL (0.13 g, 0.74 mmol) in methanol (10 mL). The resultingsolution was stirred at ambient temperature for four days. Most of thereaction solvent was decanted, and the remaining reaction mixture wasfiltered and vacuum-dried to give a white solid (1.00 g, 23% yield) thatexhibited a swell ratio of 22.8. When the swell test was repeated,allowing 19 hours for the gel to swell followed by 2 hours of dynamicsuction and 9 hours of static suction, the swell ratio was 22.4. After14 hours' exposure to ambient atmosphere, the sample retained 19.9 timesits own weight in water.

Example 32A Synthesis of Polyallylamine Crosslinked withN,N′-Bis(ethoxycarbonylmethyl)-D-glucaramide

Preparation was conducted in a drybox with oven-dried glassware.Polyallylamine hydrochloride (MW ca. 60,000, 6.55 g, 70.0 mmol) wasweighed into a 500-mL round-bottom flask equipped with a magneticstirbar. Methanol (270 mL) was added and the solution was treated withneat triethylamine (11.7 mL, 84.0 mmol) followed by a slurry ofN,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.25 g, 0.69 mmol) inmethanol (20 mL). The resulting solution was stirred at ambienttemperature for four days. The reaction solvent was removed undervacuum, and the oily solid was washed repeatedly with methanol (180 mL).Addition of pentane (50 mL) to a methanol slurry (ca. 20 mL volume)produced a solid that was filtered and then vacuum-dried to give a whitesolid (2.39 g, 57% yield) that exhibited a swell ratio (after 29 minutesof suction) of 62.8. When the swell test was repeated, allowing 16 hoursfor the gel to swell followed by 34 minutes of suction, the swell ratiowas 118.9. After 23 hours' exposure to ambient atmosphere, the sampleretained 108.6 times its own weight in water.

Example 32B Synthesis of Polyallylamine Crosslinked withN,N′-Bis(ethoxycarbonylmethyl)-D-glucaramide

To 23.03 g (0.2463 mole of amine groups) of poly(allylaminehydrochloride), M_(w) 60,000, in 950 mL of dry methanol in a 2-Lround-bottom flask under nitrogen were added 41.2 mL (0.296 mole) oftriethylamine over 30 minutes. A slurry ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide in a total of 65 mL of drymethanol was then added. The mixture was stirred at ambient temperaturefor 5 days and then concentrated under reduced pressure to about 150 mL.The resulting solid was separated from the methanol, washed repeatedlywith methanol and then dried under vacuum to give 12.92 g (88% yield) ofhydrogel that exhibited a swell factor of 125.

Example 33

Polyallylamine hydrochloride (MW ca. 60,000, 2.84 g, 30.4 mmol) wasweighed into 100-mL round-bottom flask equipped with a magnetic stirbar.Water (16 mL) was added and the solution was treated with an aqueous (4mL) solution of sodium hydroxide (0.27 g, 6.67 mmol) followed by asolution of GDL (0.58 g. 3.34 mmol) in water (10 mL). The reactionsolution was stirred overnight at ambient temperature resulting in agel-like mixture. The gel was washed with four 50-mL portions ofmethanol and then vacuum-dried to give a white solid (2.26 g, 69% yield)that exhibited a swell ratio (after 2 hours of suction) of 186.5. After3 additional days' exposure to static suction, the sample retained 67.9times its own weight in water. When the swell test was repeated with thesame sample, allowing 5 hours for the gel to swell followed by 2 hoursof dynamic suction and 24 hours of static suction, the swell ratio was206.0. After 3 and 8 days' additional exposure to static suction, thesample retained 173.8 and 65.5 times its own weight in water,respectively.

Example 34

Preparation was conducted under nitrogen atmosphere with oven-driedglassware. Polyallylamine hydrochloride (MW ca. 60,000, 1.01 g, 10.8mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar, and water (2 mL) was added. Dropwise addition to theslurry of an aqueous solution (1.0 mL) of sodium hydroxide (0.033 g,0.83 mmol) resulted in a viscous solution. A solution ofN,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.41 mmol) inwater (1.5 mL) was added, and the resulting solution was stirred atambient temperature for 45 hours. Solvent was removed under vacuum fromthe gelled reaction mixture, and the solid was washed with methanol (125mL) to remove sodium chloride. Vacuum-drying gave a white solid (0.98 g,89% yield) that exhibited a swell ratio (after 5 minutes of dynamicsuction and 45 minutes of static suction) of 105.8. After 2 days'exposure to ambient atmosphere, the sample retained 96.5 times its ownweight in water. When the swell test was repeated with the same sample,allowing 4.5 hours for the gel to swell followed by 5 hours of dynamicsuction and hours of static suction, the swell ratio was 197.6. After 6days' exposure to ambient atmosphere, the sample retained 167.8 timesits own weight in water.

Example 35

Polyethylenimine (M_(n)=ca. 10,000, M_(w)=ca. 25,000, Aldrich 408727,0.74 g, 17.2 mmol) was weighed into a 20-mL scintillation vial equippedwith a magnetic stirbar, and methanol (4.5 mL) was added. Concentratedhydrochloric acid (0.72 mL, 8.65 mmol) was added to the reactionsolution dropwise over ca. one minute and the mixture was stirred atambient temperature for 3 hours. A solution of GDL (0.15 g, 0.862 mmol)in methanol (1 mL) was added dropwise over ca. one minute to thereaction solution. The reaction mixture began to gel after 3 hours, butstirring was continued for 24 hours. The solvent was removed undervacuum and the solid was vacuum-dried to give a yellow solid (ca. 0.2 g)that exhibited a swell ratio (after 1 hour of static suction) of 24.1.After 5 days' exposure to ambient atmosphere, the sample retained 9.2times its own weight in water. When the swell test was repeated with thesame sample, allowing 7.5 hours for the gel to swell followed by 35minutes of dynamic suction, the swell ratio was 36.6. After 1 day'sexposure to ambient atmosphere, the sample retained 34.2 times its ownweight in water.

Example 36

Polyethylenimine (M_(n)=ca. 10,000, M_(w)=ca. 25,000, Aldrich 408727,0.67 g, 15.6 mmol) was weighed into a 20-mL scintillation vial equippedwith a magnetic stirbar, and water (2.5 mL) was added. Concentratedhydrochloric acid (0.65 mL) was added dropwise to the solution followedby solid N,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.39mmol) and water (1 mL). The reaction solution was stirred for 5 days atambient temperature. The solvent was then removed under vacuum, and thesolid was vacuum-dried to give a colorless solid that exhibited a swellratio (after 50 minutes of dynamic suction and 15 minutes of staticsuction) of 17.6. When the swell test was repeated with the same sample,allowing 15 hours for the gel to swell followed by 2.25 hours ofsuction, the swell ratio was 25.5. After five days' exposure to ambientatmosphere, the sample retained 22.8 times its own weight in water.

Example 37 Biocidal Activity of Crosslinked Hydrogels

Antimicrobial activity was determined by a standard micro-shake flasktest. Bacterial cultures were inoculated into TSB (Trypticase Soy Broth)and incubated at 37° C. overnight for 20+/−2 hours. The following day,the concentration of bacteria was adjusted to ˜1.0×10⁵ cfu/mL(cfu=colony forming unit) by dilution with 0.6 mM phosphate buffer.Diluted bacterial culture (2.5 mL) was then transferred into cultureplate wells containing 2.5 mL of hydrogel (˜50 mg of solid dispersed in2.5 mL of 0.6 mM phosphate buffer) or just 2.5 mL of 0.6 mM phosphatebuffer (control). The culture plates were incubated at room temperatureon a platform shaker with constant shaking motion. Three 100-μL aliquotswere periodically removed from each well and serially diluted with 0.6mM phosphate buffer. Undiluted and diluted samples from each well wereplated onto duplicate TSA (trypticase soy agar) plates, and incubated at37° C. for 20±2 hrs. After incubation, the number of bacterial colonieson each plate was counted using a Q-count instrument or equivalentcounting method. The colony count was averaged and normalized bycorrecting for the dilution factor and reported as the number of colonyforming units (cfu) per mL. Log reduction (log rd×n)=(mean log₁₀ densityof microbes in flasks of untreated control samples)−(mean log₁₀ densityof microbes in flasks of treated samples).

Microbes tested were Escherichia coli, Pseudomonas aeruginosa,Stapphylococcus aureus, and Candida albicans.

Three hydrogel samples were tested for antimicrobial activity: Sample Awas prepared as in Example 29. Sample B was prepared in the manner ofExample 30A. Sample C was prepared as in Example 31. Results are inTable 4.

TABLE 4 Biocidal Activity of Crosslinked Hydrogels sample inoculum A B Chydrogel, (control) log log log log log log microbe t, h wt % log cfucfu rdxn cfu rdxn cfu rdxn E. coli 4 1.0 4.86 1.37 3.49 0.00 4.86 0.004.86 0.50 4.86 1.73 3.13 0.00 4.86 0.00 4.86 0.25 4.86 1.70 3.16 0.004.86 0.00 4.86 0.10 4.86 2.22 2.64 0.00 4.86 0.00 4.86 24 1.0 4.86 0.004.86 0.50 4.86 0.00 4.86 0.25 4.86 0.00 4.86 0.10 4.86 0.00 4.86 P.aeruginosa 4 1.0 4.86 0.00 4.86 0.00 4.86 0.00 4.86 0.50 4.86 0.00 4.860.00 4.86 0.00 4.86 0.25 4.86 0.00 4.86 0.00 4.86 0.00 4.86 0.10 4.860.00 4.86 0.00 4.86 0.00 4.86 S. aureus 4 1.0 4.66 3.94 0.72 0.00 4.660.00 4.66 0.50 4.66 3.92 0.74 0.00 4.66 0.00 4.66 0.25 4.66 3.51 1.150.00 4.66 0.00 4.66 0.10 4.66 3.47 1.19 0.00 4.66 0.00 4.66 24 1.0 4.662.40 2.26 0.50 4.66 1.37 3.29 0.25 4.66 1.18 3.49 0.10 4.66 1.67 2.99 C.albicans 4 1.0 5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.50 5.09 0.00 5.090.00 5.09 0.00 5.09 0.25 5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.10 5.091.92 3.17 0.00 5.09 0.00 5.09

Example 38 Emulsion Prepared Using Hydrogel Prepared from PolyallylamineHCl. GDL, and Jeffamine® EDR-192

A crosslinked hydrogel was prepared in the following manner: 28.0 g(0.30 equiv of polyallylamine hydrochloride was dissolved in 200 mL ofwater along with 2.4 g (0.06 mol) of sodium hydroxide. To that solutionwas added a solution of 5.2 g (0.030 mol) of GDL and 2.9 g (0.015 mol)of Jeffamine® EDR-192 dissolved in 100 mL of water. The mixture was thenheated to 50° C. Within 1 hour, a gelled product had formed. The gel wasleft to “cure” overnight at room temperature. It was then filtered andwashed 3 times with MeOH/THF. The remaining polymer was then dried in avacuum oven at 80° C. to yield 20.63 g (61%) of a white granularmaterial. The polymer exhibited a swell ratio of 81.

An emulsion was prepared using 2.0 g of the polymer prepared above, 17.0g of octyl palmitate, and 148 mL of water. These ingredients were addedto a 250-mL beaker and emulsified using a Silverson Lab Mixer equippedwith a rotor-stator square-holed blade running at 5,000 rpm for 5 min. Athick, creamy white emulsion was prepared. After 8 months' storage in ajar at room temperature, separation of the emulsion was negligible.

Example 39 Preparation of Crosslinked Polymer using Poly(methacryloylchloride), GDL, and Ethylenediamine

Into a 250-mL 3-necked round-bottom flask equipped with a heatingmantle, reflux condenser, nitrogen inlet, and overhead stirrer was addeda 25 mL of dioxane containing 6.25 g (0.598 equivalent) ofpoly(methacryloyl chloride) (Polysciences, Inc., Warrington, Pa.). Tothis solution was added 3.5 g (0.0150 mol) ofN,N′-bis(2-aminoethyl)-D-glucaramide (prepared by reacting 10equivalents of ethylenediamine with GDL in DMAC at 50° C. and isolatingthe product as a white precipitate). The mixture was stirred and heatedat 50° C. over a period of 21 hours. During this time, a slight colorchange from brown to yellow was noted; however, it did not appear thatthe diaminodiamide was ever fully solubilized in the dioxane solvent.The resulting product was poured into THF, filtered, and washed 3 timeswith THF to yield 2.65 g (27%) of a light tan solid material; Tg₁ 49.67°C.; Tg₂ 64.14° C.; T_(dec) 175° C.—onset; η_(inh) (HFIP) insol.

Example 40 Synthesis of Chitosan Crosslinked with GDL

Chitosan (Primex TM-656, MW ca. 79,000. 95% deacetylated, 0.79 g, 4.90mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar. Water (11.5 mL) was added, and the mixture was stirredfor 15 minutes at ambient temperature. A solution of hydrochloric acid(37%, 0.29 mL, 3.45 mmol) in water (1.5 mL) was added dropwise, and theresulting viscous light yellow mixture was stirred for 15 minutes atambient temperature. A freshly prepared solution of GDL (0.09 g, 5.40mmol) in water (1.5 mL) was added dropwise, and the reaction mixture wasstirred for 38 hours at ambient temperature, resulting in a tan-coloredhomogeneous gel-like mixture. Approximately 5 mL of the solvent wasremoved under vacuum and the reaction mixture was transferred to around-bottom flask with 15 mL of tetrahydrofuran. The resultingprecipitate was washed with four 30-mL portions of tetrahydrofuran thenvacuum-dried to give a white solid (0.75 g) that had a swell ratio of 3.

Example 41 Hard Surface Disinfection by Crosslinked Hydrogels

Tests were performed by Consumer Product Testing Company, Fairfield,N.J. following Association of Official Analytical Chemists (AOAC) UseDilution test methods 955.14 and 955.15.

Hydrogel A was prepared by reacting poly(allylamine hydrochloride),M_(w) 60,000, with 0.15 mole equivalent (relative to amine groups) ofdiethyl L-tartrate according to Example 30B to give a polymer nominallyhaving 30% of its amine groups crosslinked. Hydrogel B was prepared byreacting poly(allylamine hydrochloride), M_(w) 60,000, with 0.01 moleequivalent (relative to amine groups) ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32B togive a polymer nominally having 2% of its amine groups crosslinked. Eachhydrogel was dispersed in deionized water, hydrogel A at 0.5 wt % (w/v)and hydrogel B at 1 wt % (w/v).

Type 304 stainless steel penicylinders (8 mm OD, 6 mm ID, 10 mm L) weresoaked overnight in 1 N sodium hydroxide, washed with water until therinse water was neutral to phenolphthalein, and autoclaved in 0.1% w/vaqueous asparagine solution. The sterile penicylinders were drained andtransferred aseptically into a 48-hour culture broth (1 mL per cylinder)of Staphylococcus aureus (ATCC#6538) or Salmonella choleraesuis(ATCC#10708). After being immersed in culture broth for 15 minutes, thepenicylinders were drained and transferred by sterile hook into asterile glass petri dish lined with sterile filter paper so that thecylinders stood on end without touching one another. The penicylinderswere dried at 37° C. for 40 minutes.

For each hydrogel tested, 10 penicylinders inoculated with a given testorganism were immersed individually for 10 minutes at 20° C. in 10 mL ofaqueous hydrogel dispersion. Each penicylinder was then removed from thehydrogel dispersion, drained, and deposited into a primary culture tubecontaining 10 mL of Letheen broth and incubated at 37° C. After 30minutes, each penicylinder was transferred into secondary culture tubecontaining 10 mL of Letheen broth, and both primary and secondaryculture tubes were incubated at 37° C. for 48 hours, after which theywere examined for microbial growth as evidenced by turbidity.

Neutralization of each antimicrobial hydrogel by double serialsubculture was shown to be effective by inoculating tubes showing nogrowth with low levels of test organism. Viability of test organisms wasdemonstrated by incubating inoculated penicylinders in deionized waterinstead of a hydrogel suspension.

Results in Table 5 demonstrate that hydrogel B is bactericidal againstStaphylococcus aureus. While it is also active against Salmonellacholeraesuis, hydrogel B does not completely eradicate viable Salmonellacholeraesuis under the conditions employed.

TABLE 5 Use Dilution Test Results. Number of Penicylinders ShowingResidual Microbial Activity after 10-Minute Exposure to Hydrogel testorganism Staphylococcus aureus Salmonella choleraesuis hydrogel^(a) wt%^(b) primary Secondary primary secondary A 0.5 10/10 10/10 10/10 10/10B 1.0  0/10  0/10  3/10  3/10 ^(a)See text of Example 41 fordescriptions of hydrogels A and B. ^(b)Loading of hydrogel (w/v) inaqueous dispersion.

Example 42 Preservation of a Skin Cream by a Crosslinked Hydrogel

Skin creams were formulated by mixing ingredients in the amounts listedin Table 6. The crosslinked hydrogel used was made according to Example30B. Ingredients of Phase 1 were combined and heated to 77° C.

Ingredients of Phase 2 were combined and heated to 77° C. While Phase 1was kept at 77° C. and vigorously agitated by an overhead stirrer, Phase2 was added to Phase 1. After 15 minutes of vigorous agitation at 77°C., triethanolamine was added to the mixture. After the mixture had beenvigorously agitated at 77° C. for an additional 15 to 25 minutes,external heating was discontinued, and the vigorously agitated mixturewas allowed to cool. When the temperature of the mixture reached 37 to38° C., Dow Corning 200® fluid dimethicone was added, the speed ofagitation was reduced, and the mixture was allowed to cool to roomtemperature.

TABLE 6 Skin Cream Formulations formulation Ingredient A (control) BPhase 1 deionized water 70.0 g  69.3 g  crosslinked hydrogel 0.0 g 1.0 gPhase 2 Octamethylcyclotetrasiloxane 20.0 g  19.8 g  Abil ® EM-90 cetyldimethicone copolyol 2.0 g 2.0 g Stepan TAB-2 ® 3.0 g 3.0 g Phase 3Triethanolamine 2.4 g 2.4 g Dow Corning 200 ® fluid dimethicone 2.5 g2.5 g

Ten grams of each skin cream formulation were supplemented with 500 μLof trypticase soy broth, mixed in by hand, to promote bacterial growth.Each skin cream sample was then inoculated with 100 μL of a 1:10dilution of an overnight culture of Pseudomonas aeruginosa and 100 μL ofa 1:10 dilution of an overnight culture of Staphylococcus aureus,yielding a bacterial load of approximately 1×10⁶ cfu/g for each organism(cfu=colony forming unit). Periodically, each inoculated skin cream wassampled with a 10-μL loop, which was then streaked onto a trypticase soyagar (TSA) plate. Plates were incubated at 37° C. for 24 hours and thenexamined for bacterial growth.

Results in Table 7 show that bacteria persisted in the unpreservedcontrol sample, A, but not in the sample containing crosslinkedhydrogel, B.

TABLE 7 Bacterial Growth Observed After Streaking on TSA Plates skincream formulation time, days A (control) B 0 heavy heavy 0.25 heavyheavy 1 heavy 10-100 cfu 7 moderate-heavy none

Example 42A Preservation of a Skin Cream by a Crosslinked Hydrogel

Microbiological tests were performed by Consumer Product TestingCompany, Fairfield, N.J. according to the United States Pharmacopoeia(USP), 24^(th) Edition, <51> Antimicrobial Effectiveness Testing.

Hydrogel A was prepared by reacting poly(allylamine hydrochloride),M_(w) 60,000, with 0.15 mole equivalent (relative to amine groups) ofdiethyl L-tartrate according to Example 30B to give a polymer nominallyhaving 30% of its amine groups crosslinked. Hydrogel B was prepared byreacting poly(allylamine hydrochloride), M_(w) 60,000, with 0.01 moleequivalent (relative to amine groups) ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32B togive a polymer nominally having 2% of its amine groups crosslinked.

Skin creams were formulated by mixing ingredients in the amounts listedin Table 8. Ingredients of Phase 1 were combined and heated to 77° C.Ingredients of Phase 2 were combined and heated to 77° C. While Phase 1was kept at 77° C. and vigorously agitated by an overhead stirrer, Phase2 was added to Phase 1. After 15 minutes of vigorous agitation at 77°C., triethanolamine was added to the mixture. After the mixture had beenvigorously agitated at 77° C. for an additional 15 to 25 minutes,external heating was discontinued, and the vigorously agitated mixturewas allowed to cool. When the temperature of the mixture reached 37 to38° C., Dow Corning 200® fluid dimethicone was added, the speed ofagitation was reduced, and the mixture was allowed to cool to roomtemperature.

TABLE 8 Skin Cream Formulations formulation ingredient 1 (control) 2 3Phase 1 deionized water 350.5 g  346.5 g  207.9 g  crosslinked hydrogelA —  5.0 g — crosslinked hydrogel B — — 3.0 g Phase 2octamethylcyclotetrasiloxane 100.0 g  99.0 g 59.4 g  Abil ® EM-90 cetyldimethicone 10.0 g 10.0 g 6.0 g copolyol Stepan TAB-2 ® 15.0 g 15.0 g9.0 g Phase 3 triethanolamine 12.0 g 12.0 g 7.2 g Dow Corning 200 ®fluid 12.5 g 12.5 g 7.5 g dimethicone

The microbial tests described below were performed by Consumer ProductTesting Company, Fairfield, N.J. Twenty-gram portions of each skin creamformulation were aseptically transferred into sterile glass containersand inoculated with 100 μL of a 1×10⁸ cfu/mL culture of Staphylococcusaureus (ATCC#6538), Escherichia coli (ATCC#8739), Pseudomonas aeruginosa(ATCC#9027), Candida albicans (ATCC#10231) or Aspergillus niger(ATCC#16404), yielding a microbial load between 1×10⁵ and 1×10⁶ cfu/g.Inoculated samples were incubated at 20 to 25° C. protected from light.Periodically, samples of each inoculated skin cream were seriallydiluted tenfold, and microbial counts were determined by the pour platemethod, using trypticase soy agar (TSA) plates incubated at 20 to 25° C.for 3 days for bacteria and Sabouraud dextrose agar (SDA) platesincubated at 20 to 25° C. for 5 days for the fungi.

Results in Table 9 demonstrate that the hydrogels increase the rate ofkill of gram positive (S. aureus) and gram negative (E. coli, P.aeruginosa) bacteria and yeast (C. albicans) in a skin creamformulation. No activity against mold (A. niger) was demonstrated by thetwo hydrogel compositions tested.

TABLE 9 Log (CFU/g) for Microorganisms in Skin Cream Formulations testmicroorganism S. aureus E. coli P. aeruginosa C. albicans A. niger skincream formulation day 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 0 5.91 5.91 5.916.04 6.04 6.04 5.99 5.99 5.99 5.96 5.96 5.96 5.79 5.79 5.79 7 3.34 <1 <13.88 2.57 2.46 3.70 2.15 2.60 3.56 2.28 2.08 5.08 5.20 5.04 14 2.70 <1<1 2.15 <1 <1 1.00 <1 2.43 2.67 <1 <1 5.04 5.18 4.98 28 <1 <1 <1 <1 <1<1 <1 <1 <1 2.66 <1 <1 3.45 4.15 4.58

Example 43 Human Repeat Insult Patch Test of Crosslinked Hydrogels

Hydrogel A was prepared by reacting poly(allylamine hydrochloride),M_(w) 60,000, with 0.15 mole equivalent (relative to amine groups) ofdiethyl L-tartrate according to Example 30B to give a polymer nominallyhaving 30% of its amine groups crosslinked. Hydrogel B was prepared byreacting poly(allylamine hydrochloride), M_(w) 60,000, with 0.01 moleequivalent (relative to amine groups) ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32B togive a polymer nominally having 2% of its amine groups crosslinked. Eachhydrogel was dispersed in deionized water, hydrogel A at 0.5 wt % (w/v)and hydrogel B at 0.8 wt % (w/v).

The Repeat Insult Patch Test was performed by Consumer Product TestingCompany, Fairfield, N.J. The fifty-two subjects completing this testincluded 12 men, age 32 to 68 years, and 40 women, age 22 to 79 years.Subjects had no visible skin disease, were in good health, were notpregnant or nursing, were not under a doctor's care or taking medicationthat would influence the outcome of the study, and had not used atopical or systemic steroid or antihistamine for at least seven daysprior to beginning the study.

Approximately 0.2 mL of each hydrogel dispersion, or an amountsufficient to cover the contact surface, was applied to the ¾″×¾″absorbent pad of an adhesive dressing. The dressing was then applied toa marked spot between the scapulae of each subject, thus forming anocclusive patch. Patches were applied to the same site three times aweek (typically, Monday, Wednesday, and Friday) for three consecutiveweeks (total of 9 applications). Each patch was removed after 24 hoursof contact. The site of application was examined and scored upon removalof the first patch and again 24 hours after removal of the first patch.Thereafter, the site of application was examined and scored 24 or 48hours after the removal of each patch, usually just before applicationof the subsequent patch. Thus, the application site on each subject wasexamined 10 times during the Induction Phase. Approximately 2 weeksafter application of the final Induction patch, a Challenge patch wasapplied to a virgin site adjacent to the original site, following thesame procedure as described above. The patch was removed 24 hours afterapplication, and the site was examined and scored. The Challenge sitewas examined and scored again 48 hours after removal of the Challengepatch.

Each time an Induction or Challenge site was examined, it was scoredaccording to the following scale: 0=no visible skin reaction, +=barelyperceptible or spotty erythema, 1=mild erythema covering most of thetest site, 2=moderate erythema with possible presence of mild edema,3=marked erythema with possible edema, and 4=severe erythema withpossible edema, vesiculation, bullae or ulceration. For both materialstested, all scores (10 Induction and 2 Challenge for each of 52subjects) were 0. In addition, 5 subjects who began the study butdiscontinued for various reasons not related to the test materialsgenerated scores of only 0 as well. Thus, hydrogel A and hydrogel Bshowed no dermal irritation or allergic contact sensitization.

Example 44 Speed of Kill of Crosslinked Hydrogels

Hydrogel A was prepared by reacting poly(allylamine hydrochloride),M_(w) 60,000, with 0.01 mole equivalent (relative to amine groups) ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32A togive a polymer nominally having 2% of its amine groups crosslinked.Hydrogel B was prepared by reacting poly(allylamine hydrochloride),M_(w) 60,000, with 0.15 mole equivalent (relative to amine groups) ofdiethyl L-tartrate according to Example 30A to give a polymer nominallyhaving 30% of its amine groups crosslinked. Hydrogel C was prepared byreacting poly(allylamine hydrochloride), M_(w) 60,000, with 0.25 moleequivalent (relative to amine groups) of diethyl L-tartrate according toExample 30, except using 0.900 g of poly(allylamine hydrochloride),0.192 g of sodium hydroxide, and 0.412 mL of diethyl L-tartrate andallowing the reaction to proceed for 88 hours before washing withmethanol, to give a polymer nominally having 50% of its amine groupscrosslinked.

For each hydrogel, an exposure of E. coli to a 100 ppm loading waseffected by dispersing 5 mg of hydrogel in 25 mL of 0.6 mM phosphatebuffer, stirring overnight, and then adding 25 mL of a culture broth(˜1.0×10⁵ cfu/mL) of Escherichia coli ATCC#25922. After 15, 30, 60, 120,180, and 240 minutes, aliquots of the test mixture were removed andserially diluted 1:10 with TSB in a 96-well microtiter plate. Afterincubating overnight at 37° C., each plate was scored for microbialgrowth using a Most Probable Number (MPN) protocol, and log reductioncalculated as (mean log₁₀ density of microbes in untreated controlsamples)−(mean log₁₀ MPN density of microbes in treated samples).

Exposure of E. coli to a 10 ppm loading of each hydrogel was effectedsimilarly except using 1 mg of hydrogel in 50 mL of buffer and adding 50mL of a culture broth (˜1.0×10⁵ cfu/mL) of Escherichia coli ATCC#25922.

Results in Table 10 show that all three hydrogels eliminate viable E.coli when present at 100 ppm. At 10 ppm loading, it becomes moreapparent that the speed of kill of hydrogel A is faster than that ofhydrogel B, which is faster than that of hydrogel C.

TABLE 10 Speed of Kill of E. coli #25922 by Crosslinked Hydrogels logreduction of cfu/mL t, hydrogel A^(a) hydrogel B^(a) hydrogel C^(a)minutes 100 ppm 10 ppm 100 ppm 10 ppm 100 ppm 10 ppm 15 5.40 3.09 2.391.69 2.39 0.99 30 5.40 5.36 2.39 2.78 3.48 1.69 60 5.40 5.40 3.23 2.783.48 1.83 120 5.40 5.40 5.40 3.95 5.36 2.08 180 5.40 5.40 5.40 3.79 5.403.09 240 5.40 5.40 5.40 5.40 5.40 2.78 ^(a)See text of Example 44 fordescriptions of hydrogels A, B, and C.

What is claimed is:
 1. An antimicrobial composition comprising: anantimicrobial agent which is a crosslinked polymer, the crosslinkedpolymer comprising: A) a linear, branched or cyclic polymeric backbonecomprising repeat units that comprise one or more groups selected from:hydrocarbylene groups selected from one or more aliphatic, aromatic,linear, branched, or cyclic groups; heteroatoms; and carbonyl groups;and B) one or more crosslinking units that include at least one aldaroylstructural unit of Formula I:

where n is 1-6; wherein the hydrocarbylene groups and heteroatoms of therepeat units are optionally substituted with substituents that compriseone or more of C₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonylcarbon groups, and wherein the hydrocarbylene groups of the substituentsare aliphatic or aromatic, linear, branched, or cyclic, or combinationsthereof.
 2. The antimicrobial composition of claim 1 wherein thepolymeric backbone of the crosslinked polymer comprises optionallysubstituted —NZ—, —N+ZZ′—, —O—, —C(═O)NZ—, —C(═O)O—, —C(═O)—, —OC(═O)O—,—OC(═O)NZ—, —NHC(═O)NZ—, or —SiZZ′O— linkages, wherein Z and Z′ areindependently hydrogen, alkyl, substituted alkyl, aryl, or substitutedaryl.
 3. The antimicrobial composition of claim 1 wherein thesubstituents on the hydrocarbylene groups and heteroatoms of the repeatunits of the crosslinked polymer comprise one or more of: —X, —O(Z),—N(ZZ′), —N+(ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O, —O—, —N(Z),—N+(ZZ′)—, —C(═O)N(Z)—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)N(Z)—,—N(Z)C(═O)N(Z′)—, —C(═O)NH(CH₂)pNH2, —Si(ZZ′)O—, —(OCH2CH2)mOH, or—(OSi(ZZ′))nOH, and salts thereof, wherein X is a halogen, Z, Z′, and Z″are independently hydrogen or C1-C22 alkyl, substituted alkyl, aryl, orsubstituted aryl, and wherein m is 1 to 50, n is 1 to 100, and p is 1 to12.
 4. The antimicrobial composition of claim 3 wherein the repeat unitsof the crosslinked polymer comprise aliphatic hydrocarbylene groupshaving substituents comprising one or more of C₁-C₂₂ aminoalkyl groups,—C(═O)OZ, —C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH₂)_(p)NH₂, and saltsthereof.
 5. The antimicrobial composition of claim 1 wherein at leastone repeat unit of the crosslinked polymer is an azahydrocarbylene orsalt thereof, comprising a nitrogen atom having one or more terminalaminoalkyl groups or salts thereof as substituents.
 6. The antimicrobialcomposition of claim 1 wherein at least one repeat unit of thecrosslinked polymer contains one or more substituents comprising one ormore of C1-C22 aminoalkyl groups, optionally substituted with alkyl oraldaroyl groups, or a salt thereof.
 7. The antimicrobial composition ofclaim 1 wherein the crosslinked polymer is a derivative ofpolyallylamine, polyallylamine hydrochloride, branchedpolyethyleneimine, branched polyethyleneimine hydrochloride,poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(□-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or a derivativeor salt thereof.
 8. The antimicrobial composition of claim 1 wherein thealdaroyl moiety in the crosslinking unit is glucaroyl, galactaroyl,mannaroyl, xylaroyl, or tartaroyl.
 9. The antimicrobial composition ofclaim 1 wherein the crosslinking unit comprises one or more groupsselected from groups having Formulae II, III, IV, and V

wherein Q is —O— or —NH—, or a salt thereof, and R₁, R₂, R₃ and R₄ arealiphatic or aromatic hydrocarbylene groups, linear, branched or cyclic,optionally substituted, and optionally containing —O—, —Si(ZZ′)O—,—(C═O)— or —NZ— linkages, where Z and Z′ are independently hydrogen,alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, orsubstituted aryl; and wherein the group having Formulae II, III, IV, orV is directly attached to the polymer backbone.
 10. The crosslinkedpolymer of claim 9 wherein: R₁ is —[(CH₂)₀₋₂₂]—,—(CH₂)_(a)C₆H₁₀(CH₂)_(b)—, —(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,—[(CH₂CH(Z′)O)₁₋₂₂(CH₂)₂₋₃]— wherein Z′ is H or CH₃, —C(O)NH(CH₂)₂₋₂₂—,or —(CH₂)_(a)(C₆H₄)(CH₂)_(b)—, wherein a=0-6 and b=0-6; R₂ is—[(CH₂)₁₋₂₁]—, —CH(CH₃)—, —CH(isopropyl)-, —CH(isobutyl)-,—CH(CH(CH₃)CH₂CH₃)—, —CH(CH₂OH)—, —CH(CH₂CH₂SCH₃)—, —CH(CH(OH)CH₃)—,—CH(CH₂C₆H₅)—, —CH(CH₂C₆H₄OH)—, —CH(CH₂CONH₂)—, or —CH(CH₂CH₂CONH₂)—; R₃is —[(CH₂)₂₋₂₂]—, —[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—, —[(CH₂)₀₋₆C₆H₄(CH₂)₀₋₆]—,—[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—, —[CH₂CH(CH₃)[OCH₂CH(CH₃CH)]₁₋₂₁]—,—(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,—[CH₂CH(CH₃)[OCH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z)]— whereinx+y+z=2-50, —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)_(z)]—wherein x+y+z=2-50,—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—wherein x+y+z=2-10 and Z′ is H, methyl or ethyl,—[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y))CH₂[OCH₂CH(CH₃)]_(z)— whereinx+y+z=3-100, or —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)— orsalts thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionallysubstituted alkyl, aryl, or alkaryl; and R₄ is —C(═O)—, —C₆H₄CH₂—,—(CH₂)₁₋₂₂Y′CH₂CH(OH)CH₂—, or —(CH₂)₁₋₂₂Y′C(O)CH(OH)CH₂—, wherein Y′ isO or NH.
 11. The antimicrobial composition of claim 1 wherein about 0.1%to about 100% of the polymer backbone repeat units are connected to acrosslinking unit.
 12. The antimicrobial composition of claim 11 whereinabout 1% to about 30% of the polymer backbone repeat units are connectedto a crosslinking unit.
 13. An antimicrobial composition comprising: anemulsifying agent which is a crosslinked polymer prepared by a processcomprising the step of contacting a crosslinking agent with a substratepolymer to form a crosslinked polymer; wherein the crosslinking agenthas Formula VI, VII or VIII:

wherein L and L′ independently contain a suitable functional group, andn=1-6, m=0-4, and p=1-4; and the substrate polymer comprises: A) alinear, branched or cyclic polymeric backbone comprising repeat unitsthat comprise one or more of hydrocarbylene groups, heteroatoms, andcarbonyl carbon groups; wherein the hydrocarbylene are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof; andwherein the hydrocarbylene groups and heteroatoms of the repeat unitsare optionally substituted with substituents that comprise one or moreof C₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonyl carbongroups, wherein the hydrocarbylene groups of the substituents arealiphatic or aromatic, linear, branched, or cyclic, or combinationsthereof; and B) reactive pendant groups attached to the polymericbackbone, the pendant groups being of the formula -G or —R-G, wherein Gis a nucleophile or electrophile; wherein R is independently linear,cyclic, or branched alkylene, arylene, or alkarylene groups of 1-22carbon atoms, optionally substituted with alkyl, aryl, hydroxy, amino,carbonyl, ester, amide, alkoxy, nitrile or halogen, and optionallycontaining —O—, —Si(ZZ′)O—, —(C═O)— or —NZ— linkages, where Z and Z′ areindependently hydrogen, alkyl, substituted alkyl, alkaryl, substitutedalkaryl, aryl, or substituted aryl.
 14. The antimicrobial composition ofclaim 13 wherein the suitable functional group of the crosslinkedpolymer is derived from an amine, hydroxyl, carboxylic acid, ester,urethane, urea, amide, or isocyanate; and G is an epoxide, isocyanate,benzylic halide, amine, acid halide, ester, or amide.
 15. Theantimicrobial composition of claim 13 wherein L and L′ are independentlyselected from —Y—R, wherein Y is O, NH, or S and R is alkyl, substitutedalkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.
 16. Theantimicrobial composition of claim 13 wherein L and L′ are independentlyselected from optionally substituted —NHR″, —OH, and —C(═O)OR″; and G isselected from —NH₂, —C(═O)Cl, —C(═O)OR″, or —C(═O)NH—R″—NH₂, wherein R″is independently hydrogen or an optionally substituted hydrocarbyl orhydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3.
 17. Theantimicrobial composition of claim 13 wherein less than 100% of thereactive pendant groups are derivatized to be substantially unreactiveto the crosslinking agent, wherein the derivatization is performedeither before, during or after contact of the crosslinker with thepolymer substrate.
 18. The antimicrobial composition of claim 13 whereinthe reactive pendant groups are derivatized before the contacting of thecrosslinker with the polymer substrate.
 19. The antimicrobialcomposition of claim 13 wherein the reactive pendant groups arederivatized to contain an optionally substituted aliphatic carbon chainwith optional —(NZ)—, and —O— linkages, where Z is hydrogen, optionallysubstituted alkyl or optionally substituted aryl.
 20. The antimicrobialcomposition of claim 13 wherein the reactive pendant groups arederivatized to contain a linear or branched alkyl group of 1-22 carbonatoms, optionally substituted with —O— linkages, and optionallysubstituted with —NH₂, halogen, hydroxyl, or carbonyl groups, or saltthereof.
 21. The antimicrobial composition of claim 13 wherein G is —NH₂and the reactive pendant groups are derivatized with a C₁-C₂₂ alkylgroup.
 22. The antimicrobial composition of claim 13 wherein up to about50% of the reactive pendent groups are derivatized.
 23. Theantimicrobial composition of claim 13 wherein up to about 20% of thereactive pendent groups are derivatized.
 24. The antimicrobialcomposition of claim 13 wherein the polymeric backbone comprises atleast one selected from: —NZ—, —N⁺ZZ′—, —O—, —C(═O)NZ—, —C(═O)O—,—C(═O)—, —OC(═O)O—, —OC(═O)NZ—, —NHC(═O)NZ—, or —SiZZ′O— linkages, whereZ and Z′ are independently hydrogen, alkyl, substituted alkyl, aryl, andsubstituted aryl.
 25. The antimicrobial composition of claim 13 whereinthe repeat units of the substrate polymer comprise aliphatichydrocarbylene groups with one or more substituents comprising one ormore of aminoalkyl groups, —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, or—C(═O)NH(CH₂)_(n)NH₂, or salts thereof, where X is halogen, Z and Z′ areindependently hydrogen, C₁-C₂₂ alkyl, substituted alkyl, aryl, orsubstituted aryl, and n=1-12.
 26. The antimicrobial composition of claim13 wherein substituents on the repeat units are one or more of —X,—O(Z), —N(ZZ′), —N⁺(ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O, —O—,—N(Z)—, —N⁺(ZZ′)—, —C(═O)N(Z)—, —C(═O)O—, —C(═O)—, —OC(═O)O—,—OC(═O)N(Z)—, —N(Z)C(═O)N(Z′)—, —C(═O)NH(CH₂)_(p)NH₂, —Si(ZZ′)O—,—(OCH₂CH₂)_(m)OH, or —(OSi(ZZ′))_(n)OH, or salts thereof, wherein X is ahalogen, Z, Z′, and Z″ are independently hydrogen or C₁-C₂₂ optionallysubstituted alkyl or aryl, and wherein m is 1 to 50, n is 1 to 100, andp is 1 to
 12. 27. The antimicrobial composition of claim 13 wherein therepeat units contain substituents comprising one or more of C₁-C₂₂aminoalkyl groups, optionally substituted with alkyl or aldaroyl groups,or salts thereof.
 28. The antimicrobial composition of claim 13 whereinat least one repeat unit is an azahydrocarbylene or salt thereof,comprising a nitrogen atom having one or more terminal aminoalkyl groupsor salts thereof as substituents.
 29. The antimicrobial composition ofclaim 13 wherein the substrate polymer comprises polyallylamine,polyallylamine hydrochloride, branched polyethyleneimine, branchedpolyethyleneimine hydrochloride, poly(acryloyl chloride),poly(methacryloyl chloride), poly[N-(ω-aminoalkyl)acrylamide],polyglycosamine, carboxymethylchitosan, chitosan, chitosanhydrochloride, or a derivative or salt thereof.
 30. The antimicrobialcomposition of claim 13 wherein the crosslinking agent is derived froman aldaric acid, aldarolactone, aldarodilactone, aldarolactone ester,aldaric acid monoester, aldaric acid diester, or aldaramide, or saltsthereof.
 31. The antimicrobial composition of claim 13 wherein thecrosslinking agent is derived from glucaric acid, galactaric acid,mannaric acid, xylaric acid or tartaric acid.
 32. The antimicrobialcomposition of claim 13 wherein the crosslinking agent is of theFormulae IX, X, XI, XII:

wherein A1 is independently selected from:

and salts thereof; and A2 is selected from—NH—R₅—NH——NH—R₅—O—and—O—R₅—O— and salts thereof; wherein R₅ and R₇ are independentlyaliphatic or aromatic hydrocarbylene groups, linear or cyclic,optionally substituted with alkyl, aryl, hydroxy, amino, carbonyl,carboxyl, ester, amide, alkoxy, nitrile or halogen, or slats thereof,and optionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ— linkages,where Z and Z′ are independently hydrogen, alkyl, substituted alkyl,alkaryl, substituted alkaryl, aryl, or substituted aryl; and R₆ ishydrogen or a 1-22 carbon alkyl group.
 33. The antimicrobial compositionof claim 32 wherein R₅ and R₇ are independently optionally substitutedaliphatic carbon chains with optional —(NZ)— or —O— linkages, wherein Zis hydrogen, optionally substituted alkyl or optionally substitutedaryl.
 34. The antimicrobial composition of claim 32 wherein R₅ and R₇are independently linear, cyclic, or branched alkylene groups of 1-10carbon atoms, optionally substituted with —O— linkages, and optionallysubstituted with —NH₂ groups, or salts thereof.
 35. The antimicrobialcomposition of claim 32 wherein R₇ is —[(CH₂)₁₋₂₁]—; —CH(CH₃)—;—CH(isopropyl)-; —CH(isobutyl)-; —CH(CH(CH₃)CH₂CH₃)—; —CH(CH₂OH)—;—CH(CH₂CH₂SCH₃)—; —CH(CH(OH)CH₃)—; —CH(CH₂C₆H₅)—; —CH(CH₂C₆H₄OH)—;—CH(CH₂CONH₂)—; or —CH(CH₂CH₂CONH₂)—; and R₅ is —[(CH₂)₂₋₂₂]—;—[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—; —[(CH₂)₀₋₆C₆H₄(CH₂)₀₋₆]—;—[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—; —[CH₂CH(CH₃)[OCH₂CH(CH₃)]₁₋₂₁]—;—(CH₂CH₂NH)₁₋₂₂CH₂CH₂—;—[CH₂CH(CH₃)[OCH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z)]— whereinx+y+z=2-50; —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)_(z)]—wherein x+y+z=2-50;—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—wherein x+y+z=2-10 and Z′ is H, methyl or ethyl;—[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)— whereinx+y+z=3-100; or —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)—, orsalts thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionallysubstituted alkyl, aryl, or alkaryl.
 36. The antimicrobial compositionof claim 32 wherein about 0.0005 to about 0.5 molar equivalents ofcrosslinking agent are used per reactive pendant group.
 37. Theantimicrobial composition of claim 32 wherein from about 0.005 to about0.5 molar equivalents of crosslinking agent are used per reactivependant group.
 38. The antimicrobial composition of claim 32 wherein0.01 to 0.25 molar equivalents of the reactive pendant groups arederivatized.